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Vaccines, Volume 9, Issue 3 (March 2021) – 117 articles

Cover Story (view full-size image): A safe and effective preventative or therapeutic vaccine for herpes simplex virus 2 (HSV-2) has eluded development for decades. Live-attenuated HSV-2 vaccines are attractive alternatives to previous vaccine candidates. We assessed the safety of two novel live-attenuated HSV-2 vaccine candidates, RVx201 and RVx202. Guinea pigs were inoculated vaginally or intradermally with RVx201, RvX202 (107 PFU each) or wild-type virus (105 PFU) and observed for 28 days. All animals inoculated with RVx201 or RVx202 survived. The vaccine candidates did not cause disease, did not establish latency, and elicited a neutralizing antibody response against HSV-2. Based on these results, further efficacy testing of these vaccine candidates as preventative and/or therapeutic anti-HSV-2 vaccines is merited. View this paper.
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17 pages, 3836 KiB  
Article
Synthesis of Escherichia coli OmpA Oral Nanoparticles and Evaluation of Immune Functions against the Major Etiologic Agent of Cow Mastitis
by Xiang Liu, Wei Sun, Nana Wu, Na Rong, Chao Kang, Sijie Jian, Chunlin Chen, Chen Chen and Xiaoying Zhang
Vaccines 2021, 9(3), 304; https://doi.org/10.3390/vaccines9030304 - 23 Mar 2021
Cited by 8 | Viewed by 2359
Abstract
Escherichia coli is a major etiologic agent of cow mastitis, a condition that results in huge economic losses. There is a lack of an oral vaccine for cow mastitis. Previous studies have confirmed that the outer membrane protein A (OmpA) of E. coli [...] Read more.
Escherichia coli is a major etiologic agent of cow mastitis, a condition that results in huge economic losses. There is a lack of an oral vaccine for cow mastitis. Previous studies have confirmed that the outer membrane protein A (OmpA) of E. coli is immunogenic and can be used for vaccine design. In the present study, OmpA was encapsulated into nanoparticles (NP-OmpA) for an oral vaccine for cow mastitis. Methods: OmpA was purified with Ni-NTA flow resin and encapsulated with chitosan (CS) to prepare NP-OmpA nanoparticles. The gastrointestinal tract was simulated in vitro (PBS, pH 1.2) to measure the protein release rate. The optimal preparation conditions for NP-OmpA were determined by analyzing the concentrations of OmpA and CS, magnetic mixing speed, mixing time, and the ratio of tripolyphosphate (TPP)/CS (w/w). NP-OmpA safety was assessed by function factors and histopathological examination of livers and kidneys. The immune activity of NP-OmpA was determined using qRT-PCR to assess immune-related gene expression, leukocyte phagocytosis of Staphylococcus aureus, ELISA to evaluate antiserum titer and immune recognition of E. coli, and the organ index. The immune protection function of NP-OmpA was assessed by the protection rate of NP-OmpA to E. coli in mice, qRT-PCR for inflammation-related gene expression, assay kits for antioxidant factors, and visceral injury in the histopathological sections. Results: NP-OmpA nanoparticles had a diameter of about 700 nm, loading efficiency (LE) of 79.27%, and loading capacity (LC) of 20.31%. The release rate of NP-OmpA (0~96 h) was less than 50% in vitro. The optimal preparation conditions for NP-OmpAs were OmpA protein concentration of 2 mg/mL, CS concentration of 5 mg/mL, TPP/CS (w/w) of 1:1, magnetic mixing speed of 150 r/min, and mixing time of 15 min. Histopathological sections and clinical analytes of uric acid (UA), creatinine (Cr), alanine aminotransferase (ALT), aspartate transaminase (AST), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) showed NP-OmpA did not damage mice livers or kidneys. NP-OmpA could enhance the immune-related gene expression of IFN-γ and HSP70 in the spleen, liver, and kidney and the leukocyte phagocytosis of S. aureus. The antiserum titer (1:3200) was obtained from mice immunized with NP-OmpA, which had an immune recognition effect to E. coli. The immune protection rate of NP-OmpA was 71.43% (p < 0.05) to E. coli. NP-OmpA could down-regulate the inflammation-related gene expression of TNF-a, IL-6, and IL-10 in the spleen, liver, and kidney, and the antioxidant factors MDA and SOD in the liver, and reduce injury in the liver and kidney of mice induced by E. coli. Conclusions: A novel NP-OmpA nanoparticle was encapsulated, and the optimal preparation conditions were determined. The NP-OmpA was safe and had good immune functions. They are expected to induce a response that resists infection with the major etiologic agent (E. coli) of cow mastitis. Full article
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16 pages, 914 KiB  
Review
Pruritus as a Distinctive Feature of Type 2 Inflammation
by Simone Garcovich, Martina Maurelli, Paolo Gisondi, Ketty Peris, Gil Yosipovitch and Giampiero Girolomoni
Vaccines 2021, 9(3), 303; https://doi.org/10.3390/vaccines9030303 - 23 Mar 2021
Cited by 67 | Viewed by 10527
Abstract
Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in [...] Read more.
Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface. Full article
(This article belongs to the Section Clinical Immunology)
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16 pages, 1848 KiB  
Article
Vaccine Efficacy of Self-Assembled Multimeric Protein Scaffold Particles Displaying the Glycoprotein Gn Head Domain of Rift Valley Fever Virus
by Paul J. Wichgers Schreur, Mirriam Tacken, Benjamin Gutjahr, Markus Keller, Lucien van Keulen, Jet Kant, Sandra van de Water, Yanyin Lin, Martin Eiden, Melanie Rissmann, Felicitas von Arnim, Rebecca König, Alexander Brix, Catherine Charreyre, Jean-Christophe Audonnet, Martin H. Groschup and Jeroen Kortekaas
Vaccines 2021, 9(3), 301; https://doi.org/10.3390/vaccines9030301 - 23 Mar 2021
Cited by 14 | Viewed by 3867
Abstract
Compared to free antigens, antigens immobilized on scaffolds, such as nanoparticles, generally show improved immunogenicity. Conventionally, antigens are conjugated to scaffolds through genetic fusion or chemical conjugation, which may result in impaired assembly or heterogeneous binding and orientation of the antigens. By combining [...] Read more.
Compared to free antigens, antigens immobilized on scaffolds, such as nanoparticles, generally show improved immunogenicity. Conventionally, antigens are conjugated to scaffolds through genetic fusion or chemical conjugation, which may result in impaired assembly or heterogeneous binding and orientation of the antigens. By combining two emerging technologies—i.e., self-assembling multimeric protein scaffold particles (MPSPs) and bacterial superglue—these shortcomings can be overcome and antigens can be bound on particles in their native conformation. In the present work, we assessed whether this technology could improve the immunogenicity of a candidate subunit vaccine against the zoonotic Rift Valley fever virus (RVFV). For this, the head domain of glycoprotein Gn, a known target of neutralizing antibodies, was coupled on various MPSPs to further assess immunogenicity and efficacy in vivo. The results showed that the Gn head domain, when bound to the lumazine synthase-based MPSP, reduced mortality in a lethal mouse model and protected lambs, the most susceptible RVFV target animals, from viremia and clinical signs after immunization. Furthermore, the same subunit coupled to two other MPSPs (Geobacillus stearothermophilus E2 or a modified KDPG Aldolase) provided full protection in lambs as well. Full article
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14 pages, 7308 KiB  
Article
Factors Associated with COVID-19 Vaccine Hesitancy
by Patricia Soares, João Victor Rocha, Marta Moniz, Ana Gama, Pedro Almeida Laires, Ana Rita Pedro, Sónia Dias, Andreia Leite and Carla Nunes
Vaccines 2021, 9(3), 300; https://doi.org/10.3390/vaccines9030300 - 22 Mar 2021
Cited by 394 | Viewed by 51355
Abstract
It is critical to develop tailored strategies to increase acceptability of the COVID-19 vaccine and decrease hesitancy. Hence, this study aims to assess and identify factors associated with COVID-19 vaccine hesitancy in Portugal. We used data from a community-based survey, “COVID-19 Barometer: Social [...] Read more.
It is critical to develop tailored strategies to increase acceptability of the COVID-19 vaccine and decrease hesitancy. Hence, this study aims to assess and identify factors associated with COVID-19 vaccine hesitancy in Portugal. We used data from a community-based survey, “COVID-19 Barometer: Social Opinion”, which includes data regarding intention to take COVID-19 vaccines, health status, and risk perception in Portugal from September 2020 to January 2021. We used multinomial regression to identify factors associated with intention to delay or refuse to take COVID-19 vaccines. COVID-19 vaccine hesitancy in Portugal was high: 56% would wait and 9% refuse. Several factors were associated with both refusal and delay: being younger, loss of income during the pandemic, no intention of taking the flu vaccine, low confidence in the COVID-19 vaccine and the health service response during the pandemic, worse perception of government measures, perception of the information provided as inconsistent and contradictory, and answering the questionnaire before the release of information regarding the safety and efficacy of COVID-19 vaccines. It is crucial to build confidence in the COVID-19 vaccine as its perceived safety and efficacy were strongly associated with intention to take the vaccine. Governments and health authorities should improve communication and increase trust. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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17 pages, 1898 KiB  
Article
Low Adenovirus Vaccine Doses Administered to Skin Using Microneedle Patches Induce Better Functional Antibody Immunogenicity as Compared to Systemic Injection
by Olivia Flynn, Kate Dillane, Juliane Sousa Lanza, Jennifer M. Marshall, Jing Jin, Sarah E. Silk, Simon J. Draper and Anne C. Moore
Vaccines 2021, 9(3), 299; https://doi.org/10.3390/vaccines9030299 - 22 Mar 2021
Cited by 14 | Viewed by 3357
Abstract
Adenovirus-based vaccines are demonstrating promising clinical potential for multiple infectious diseases, including COVID-19. However, the immunogenicity of the vector itself decreases its effectiveness as a boosting vaccine due to the induction of strong anti-vector neutralizing immunity. Here we determined how dissolvable microneedle patches [...] Read more.
Adenovirus-based vaccines are demonstrating promising clinical potential for multiple infectious diseases, including COVID-19. However, the immunogenicity of the vector itself decreases its effectiveness as a boosting vaccine due to the induction of strong anti-vector neutralizing immunity. Here we determined how dissolvable microneedle patches (DMN) for skin immunization can overcome this issue, using a clinically-relevant adenovirus-based Plasmodium falciparum malaria vaccine, AdHu5–PfRH5, in mice. Incorporation of vaccine into patches significantly enhanced its thermostability compared to the liquid form. Conventional high dose repeated immunization by the intramuscular (IM) route induced low antigen-specific IgG titres and high anti-vector immunity. A low priming dose of vaccine, by the IM route, but more so using DMN patches, induced the most efficacious immune responses, assessed by parasite growth inhibitory activity (GIA) assays. Administration of low dose AdHu5–PfRH5 using patches to the skin, boosted by high dose IM, induced the highest antigen-specific serum IgG response after boosting, the greatest skewing of the antibody response towards the antigen and away from the vector, and the highest efficacy. This study therefore demonstrates that repeated use of the same adenovirus vaccine can be highly immunogenic towards the transgene if a low dose is used to prime the response. It also provides a method of stabilizing adenovirus vaccine, in easy-to-administer dissolvable microneedle patches, permitting storage and distribution out of cold chain. Full article
(This article belongs to the Special Issue Vaccines for Infectious and Chronic Diseases)
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16 pages, 508 KiB  
Article
The Role of Emotional Competences in Parents’ Vaccine Hesitancy
by Teresa Gavaruzzi, Marta Caserotti, Irene Leo, Alessandra Tasso, Leonardo Speri, Antonio Ferro, Elena Fretti, Anna Sannino, Enrico Rubaltelli and Lorella Lotto
Vaccines 2021, 9(3), 298; https://doi.org/10.3390/vaccines9030298 - 22 Mar 2021
Cited by 13 | Viewed by 3616
Abstract
The role of parents’ emotional competencies on vaccine hesitancy and decision making has been seldom examined. Two studies investigated the relationship between parents’ attitudes towards childhood vaccines and self-reported behavior (Study 1) and between parents’ emotional competence and attitudes towards vaccines (Study 2). [...] Read more.
The role of parents’ emotional competencies on vaccine hesitancy and decision making has been seldom examined. Two studies investigated the relationship between parents’ attitudes towards childhood vaccines and self-reported behavior (Study 1) and between parents’ emotional competence and attitudes towards vaccines (Study 2). In Study 1, predictors of temporal, partial, or complete vaccine refusal (having voluntarily postponed/forgone some/all vaccines) were examined in 2778 parents. In Study 2, psychological predictors of the attitude towards vaccines were examined in 593 parents, using the Profile of Emotional Competence and the valence of mental images spontaneously associated with the term “vaccine”. In Study 1, attitudes were aggregated in three independent factors (concerns about vaccine safety; diseases prevented by vaccines; and naturalistic views) that independently predicted vaccine refusal. In Study 2, a significant mediational analysis showed a positive indirect effect of intrapersonal emotional competences on attitudes towards vaccines, through mental images associated with the word “vaccine”. Parents’ intrapersonal emotional competences affected all dimensions of attitudes towards vaccines, suggesting that being able to manage, identify, and recognize one’s own emotions is central to vaccine acceptance. These findings suggest that intervention strategies, rather than stressing the pro-social benefits of vaccinating, should focus on aspects related to one’s own emotions. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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19 pages, 756 KiB  
Article
Measurement Invariance of the Drivers of COVID-19 Vaccination Acceptance Scale: Comparison between Taiwanese and Mainland Chinese-Speaking Populations
by Ya-Chin Yeh, I-Hua Chen, Daniel K. Ahorsu, Nai-Ying Ko, Kuan-Lin Chen, Ping-Chia Li, Cheng-Fang Yen, Chung-Ying Lin, Mark D. Griffiths and Amir H. Pakpour
Vaccines 2021, 9(3), 297; https://doi.org/10.3390/vaccines9030297 - 22 Mar 2021
Cited by 51 | Viewed by 4864
Abstract
The impacts of novel coronavirus disease-2019 (COVID-19) on human life continue to be serious. To control the spread of COVID-19, the production of effective vaccines is likely to be one of the best solutions. However, vaccination hesitancy may decrease individuals’ willingness to get [...] Read more.
The impacts of novel coronavirus disease-2019 (COVID-19) on human life continue to be serious. To control the spread of COVID-19, the production of effective vaccines is likely to be one of the best solutions. However, vaccination hesitancy may decrease individuals’ willingness to get vaccinated. The Drivers of COVID-19 Vaccination Acceptance Scale (DrVac-COVID19S) was recently developed to help healthcare professionals and researchers better understand vaccination acceptance. The present study examined whether DrVac-COVID19S is measurement invariant across different subgroups (Taiwanese vs. mainland Chinese university students; males vs. females; and health-related program majors vs. non-health-related program majors). Taiwanese (n = 761; mean age = 25.51 years; standard deviation (SD) = 6.42; 63.5% females) and mainland Chinese university students (n = 3145; mean age = 20.72 years; SD = 2.06; 50.2% females) were recruited using an online survey between 5 January and 21 February 2021. Factor structure and measurement invariance of the two DrVac-COVID19S scales (nine-item and 12-item) were tested using confirmatory factor analysis (CFA). The findings indicated that the DrVac-COVID19S had a four-factor structure and was measurement invariant across the subgroups. The DrVac-COVID19S’s four-factor structure was supported by the CFA results is a practical and valid instrument to quickly capture university students’ willingness to get COVID-19 vaccination. Moreover, the DrVac-COVID19S can be used to compare university students’ underlying reasons to get COVID-19 vaccination among different subgroups. Full article
(This article belongs to the Special Issue Vaccination and Public Health Version II: COVID-19 Vaccination)
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11 pages, 951 KiB  
Article
Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19
by Jiao Tong, Chenxi Zhu, Hanyu Lai, Chunchao Feng and Dapeng Zhou
Vaccines 2021, 9(3), 296; https://doi.org/10.3390/vaccines9030296 - 22 Mar 2021
Cited by 7 | Viewed by 3247
Abstract
The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day [...] Read more.
The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day schedule. The results showed that a Spike protein-specific antibody was induced at Day 21 with titer of above 50,000 on average, as measured by direct binding. The neutralizing titer was above 1000 on average, as determined by a pseudo-virus using monoclonal antibodies (40592-MM57 and 40591-MM43) with IC50 at 1 μg/mL as standards. The protein/peptide array-identified receptor-binding domain (RBD) was considered as immunodominant. No linear epitopes were found in the RBD, although several linear epitopes were found in the C-terminal domain right after the RBD and heptad repeat regions. Our study supports the efficacy of a recombinant trimeric Spike protein vaccine candidate for COVID-19 that is safe and ready for storage and distribution in developing countries. Full article
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11 pages, 555 KiB  
Article
Low Seroprevalence of Measles-Specific IgG in Children of Three Ethnic Groups from Mexico: Influence of Age, Sex, Malnutrition and Family Size
by Miguel A. Sánchez-Alemán, Ilse A. Gutiérrez-Pérez, Nayeli Díaz-Salgado, Oscar Zaragoza-García, María Olamendi-Portugal, Natividad Castro-Alarcón, Isela Parra-Rojas and Iris P. Guzmán-Guzmán
Vaccines 2021, 9(3), 295; https://doi.org/10.3390/vaccines9030295 - 22 Mar 2021
Cited by 5 | Viewed by 2417
Abstract
Background: The reemergence of measles represents a public health problem. The aim of the study was to determine the seroprevalence of IgG antibodies against measles in children of three ethnic groups in southern Mexico and the nutritional status and demographic risk factors associated. [...] Read more.
Background: The reemergence of measles represents a public health problem. The aim of the study was to determine the seroprevalence of IgG antibodies against measles in children of three ethnic groups in southern Mexico and the nutritional status and demographic risk factors associated. Methods: A cross-sectional study in 416 school-age children, 207 belonging to the Tlapaneco ethnic group, 101 to the Mixteco group and 108 were considered Mestizo. Sociodemographic data were collected, an anthropometric evaluation of the children was performed and a fasting blood sample was obtained from each child for the measurement of measles IgG antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). Results: From the total sample, 59% of the children were seropositive for IgG antibodies against measles; in contrast, 41% lacked IgG antibodies. Measles antibody seropositivity was higher in girls (64%). 90.5% of 6-year-old children had higher antibodies seroprevalence, compared to the children between 10 and 13 years old (45.5%). In the three ethnic groups, age was negatively correlated with the index standard ratio (ISR) of measles antibody levels and the families with ≥8 members showed less seropositivity. According to the antibodies levels, most of the positive cases remained around 1 Standard Deviation (SD) of the ISR values and no underweight children had antibody levels above 2 SD. Conclusions: The Anti-Measles serological coverage is low in children of three ethnic groups from Southern Mexico and the age, sex, malnutrition and family size are associated factors. Therefore, it is important to strengthen immunization campaigns, principally in vulnerable groups. Full article
(This article belongs to the Special Issue Measles-Mumps-Rubella-Varicella Vaccination)
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30 pages, 1332 KiB  
Review
Zika Virus Pathogenesis: A Battle for Immune Evasion
by Judith Estévez-Herrera, Silvia Pérez-Yanes, Romina Cabrera-Rodríguez, Daniel Márquez-Arce, Rodrigo Trujillo-González, José-David Machado, Ricardo Madrid and Agustín Valenzuela-Fernández
Vaccines 2021, 9(3), 294; https://doi.org/10.3390/vaccines9030294 - 22 Mar 2021
Cited by 13 | Viewed by 4613
Abstract
Zika virus (ZIKV) infection and its associated congenital and other neurological disorders, particularly microcephaly and other fetal developmental abnormalities, constitute a World Health Organization (WHO) Zika Virus Research Agenda within the WHO’s R&D Blueprint for Action to Prevent Epidemics, and continue to be [...] Read more.
Zika virus (ZIKV) infection and its associated congenital and other neurological disorders, particularly microcephaly and other fetal developmental abnormalities, constitute a World Health Organization (WHO) Zika Virus Research Agenda within the WHO’s R&D Blueprint for Action to Prevent Epidemics, and continue to be a Public Health Emergency of International Concern (PHEIC) today. ZIKV pathogenicity is initiated by viral infection and propagation across multiple placental and fetal tissue barriers, and is critically strengthened by subverting host immunity. ZIKV immune evasion involves viral non-structural proteins, genomic and non-coding RNA and microRNA (miRNA) to modulate interferon (IFN) signaling and production, interfering with intracellular signal pathways and autophagy, and promoting cellular environment changes together with secretion of cellular components to escape innate and adaptive immunity and further infect privileged immune organs/tissues such as the placenta and eyes. This review includes a description of recent advances in the understanding of the mechanisms underlying ZIKV immune modulation and evasion that strongly condition viral pathogenesis, which would certainly contribute to the development of anti-ZIKV strategies, drugs, and vaccines. Full article
(This article belongs to the Special Issue Zika Virus and Immune Response)
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17 pages, 2978 KiB  
Article
Immuno-Informatics Analysis of Pakistan-Based HCV Subtype-3a for Chimeric Polypeptide Vaccine Design
by Sajjad Ahmad, Farah Shahid, Muhammad Tahir ul Qamar, Habib ur Rehman, Sumra Wajid Abbasi, Wasim Sajjad, Saba Ismail, Faris Alrumaihi, Khaled S. Allemailem, Ahmad Almatroudi and Hafiz Fahad Ullah Saeed
Vaccines 2021, 9(3), 293; https://doi.org/10.3390/vaccines9030293 - 21 Mar 2021
Cited by 26 | Viewed by 4079
Abstract
Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in [...] Read more.
Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in curing disease. For this purpose, an immuno-informatics study is performed based on the published HCV subtype-3a from Pakistan. First, the virus genome was translated to a polyprotein followed by a subsequent prediction of T-cell epitopes. Non-allergenic, IFN-γ producer, and antigenic epitopes were shortlisted, including 5 HTL epitopes and 4 CTL, which were linked to the final vaccine by GPGPG and AAY linkers, respectively. Beta defensin was included as an adjuvant through the EAAAK linker to improve the immunogenicity of the polypeptide. To ensure its safety and immunogenicity profile, antigenicity, allergenicity, and various physiochemical attributes of the polypeptide were evaluated. Molecular docking was conducted between TLR4 and vaccine to evaluate the binding affinity and molecular interactions. For stability assessment and binding of the vaccine-TLR4 docked complex, molecular dynamics (MD) simulation and MMGBSA binding free-energy analyses were conducted. Finally, the candidate vaccine was cloned in silico to ensure its effectiveness. The current vaccine requires future experimental confirmation to validate its effectiveness. The vaccine construct produced might be useful in providing immune protection against HCV-related infections. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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10 pages, 414 KiB  
Article
COVID-19 Vaccination Willingness among Chinese Adults under the Free Vaccination Policy
by Rugang Liu, Yuxun Zhang, Stephen Nicholas, Anli Leng, Elizabeth Maitland and Jian Wang
Vaccines 2021, 9(3), 292; https://doi.org/10.3390/vaccines9030292 - 21 Mar 2021
Cited by 53 | Viewed by 5191
Abstract
(1) Background: China will provide free coronavirus disease 2019 (COVID-19) vaccinations for the entire population. This study analyzed the COVID-19 vaccination willingness rate (VWR) and its determinants under China’s free vaccination policy compared to a paid vaccine. (2) Methods: Data on 2377 respondents [...] Read more.
(1) Background: China will provide free coronavirus disease 2019 (COVID-19) vaccinations for the entire population. This study analyzed the COVID-19 vaccination willingness rate (VWR) and its determinants under China’s free vaccination policy compared to a paid vaccine. (2) Methods: Data on 2377 respondents were collected through a nationwide questionnaire survey. Multivariate ordered logistic regression models were specified to explore the correlation between the VWR and its determinants. (3) Results: China’s free vaccination policy for COVID-19 increased the VWR from 73.62% to 82.25% of the respondents. Concerns about the safety and side-effects were the primary reason for participants’ unwillingness to be vaccinated against COVID-19. Age, medical insurance and vaccine safety were significant determinants of the COVID-19 VWR for both the paid and free vaccine. Income, occupation and vaccine effectiveness were significant determinants of the COVID-19 VWR for the free vaccine. (4) Conclusions: Free vaccinations increased the COVID-19 VWR significantly. People over the age of 58 and without medical insurance should be treated as the target intervention population for improving the COVID-19 VWR. Contrary to previous research, high-income groups and professional workers should be intervention targets to improve the COVID-19 VWR. Strengthening nationwide publicity and education on COVID-19 vaccine safety and effectiveness are recommended policies for decision-makers. Full article
(This article belongs to the Special Issue Vaccination Strategies for COVID-19)
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19 pages, 2551 KiB  
Review
Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies
by Rodrigo Velázquez-Moctezuma, Elias H. Augestad, Matteo Castelli, Christina Holmboe Olesen, Nicola Clementi, Massimo Clementi, Nicasio Mancini and Jannick Prentoe
Vaccines 2021, 9(3), 291; https://doi.org/10.3390/vaccines9030291 - 20 Mar 2021
Cited by 9 | Viewed by 3805
Abstract
Hepatitis C virus (HCV) is a major causative agent of acute and chronic hepatitis. It is estimated that 400,000 people die every year from chronic HCV infection, mostly from severe liver-related diseases such as cirrhosis and liver cancer. Although HCV was discovered more [...] Read more.
Hepatitis C virus (HCV) is a major causative agent of acute and chronic hepatitis. It is estimated that 400,000 people die every year from chronic HCV infection, mostly from severe liver-related diseases such as cirrhosis and liver cancer. Although HCV was discovered more than 30 years ago, an efficient prophylactic vaccine is still missing. The HCV glycoprotein complex, E1/E2, is the principal target of neutralizing antibodies (NAbs) and, thus, is an attractive antigen for B-cell vaccine design. However, the high genetic variability of the virus necessitates the identification of conserved epitopes. Moreover, the high intrinsic mutational capacity of HCV allows the virus to continually escape broadly NAbs (bNAbs), which is likely to cause issues with vaccine-resistant variants. Several studies have assessed the barrier-to-resistance of vaccine-relevant bNAbs in vivo and in vitro. Interestingly, recent studies have suggested that escape substitutions can confer antibody resistance not only by direct modification of the epitope but indirectly through allosteric effects, which can be grouped based on the breadth of these effects on antibody susceptibility. In this review, we summarize the current understanding of HCV-specific NAbs, with a special focus on vaccine-relevant bNAbs and their targets. We highlight antibody escape studies pointing out the different methodologies and the escape mutations identified thus far. Finally, we analyze the antibody escape mechanisms of envelope protein escape substitutions and polymorphisms according to the most recent evidence in the HCV field. The accumulated knowledge in identifying bNAb epitopes as well as assessing barriers to resistance and elucidating relevant escape mechanisms may prove critical in the successful development of an HCV B-cell vaccine. Full article
(This article belongs to the Special Issue Advances in Vaccine Development)
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9 pages, 429 KiB  
Article
The Impact of a Single Educational Lecture on the Vaccine Confidence among Pregnant Women and Young Mothers
by Katarzyna Tkaczyszyn, Ernest Kuchar, Ewa Augustynowicz and Leszek Szenborn
Vaccines 2021, 9(3), 290; https://doi.org/10.3390/vaccines9030290 - 20 Mar 2021
Cited by 4 | Viewed by 1893
Abstract
Background: We investigated the impact of a single unstructured educational lecture about vaccinations on the vaccine confidence in volunteer participants. Methods: We conducted a survey-based study during a series of open meetings related to pregnancy and parenting. Before and after the pediatrician’s lecture [...] Read more.
Background: We investigated the impact of a single unstructured educational lecture about vaccinations on the vaccine confidence in volunteer participants. Methods: We conducted a survey-based study during a series of open meetings related to pregnancy and parenting. Before and after the pediatrician’s lecture related to vaccinations, listeners completed the visual analogue scales (VAS, 0–15 cm), evaluating (1) self-declared knowledge on vaccinations and (2) how they perceive the safety and efficacy of this preventive method. Results: In total, 484 women aged 30 ± 4 years participated in the lecture (pregnant = 68%; ≥1 children = 56%). Participants declared to have more comprehensive knowledge on preventive vaccinations and perceived vaccines to be safer and more useful (the role for the immunity) after vs. before the lecture (median VAS: 10.4 vs. 7.2, 10.8 vs. 8.7, and 11.0 vs. 10.4 cm, all p < 0.001). Importantly, the prevalence of vaccine-related adverse events was also assessed as being higher after the lecture (median VAS: 9.9 vs. 8.0 cm, p < 0.001). The increase in self-declared knowledge on vaccinations and perceived need for vaccinations (delta VAS—VAS after minus before the lecture, expressed as % of baseline) was lower among participants who rated the lecture less vs. more useful. Importantly, both participants who liked vs. did not like the lecture comparably rated vaccines safer after vs. before the lecture (delta VAS (median, interquartile range): 16% (0–39%) vs. 18% (2–42%), p = 0.39). Conclusions: An educational lecture on vaccinations positively impacts vaccine confidence in young adult women. Irrespective of the subjective rating of the lecture, all listeners perceived vaccinations to be safer after vs. before the speech. Full article
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14 pages, 1725 KiB  
Article
Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?
by Elena Pettini, Gabiria Pastore, Fabio Fiorino, Donata Medaglini and Annalisa Ciabattini
Vaccines 2021, 9(3), 289; https://doi.org/10.3390/vaccines9030289 - 20 Mar 2021
Cited by 14 | Viewed by 4833
Abstract
Characterizing the impact of the vaccination schedule on the induction of B and T cell immune responses is critical for improving vaccine immunogenicity. Here we compare the effect of a short (4 weeks) or a long (18 weeks) interval between priming and boosting [...] Read more.
Characterizing the impact of the vaccination schedule on the induction of B and T cell immune responses is critical for improving vaccine immunogenicity. Here we compare the effect of a short (4 weeks) or a long (18 weeks) interval between priming and boosting in mice, using a model vaccine formulation based on the chimeric tuberculosis vaccine antigen H56 combined with alum. While no significant difference was observed in serum antigen-specific IgG response and the induction of antigen-specific T follicular helper cells into draining lymph nodes after the two immunization schedules, a longer interval between priming and boosting elicited a higher number of germinal center-B cells and H56-specific antibody-secreting cells and modulated the effector function of reactivated CD4+ T cells. These data show that the scheduling of the booster immunization could affect the immune response elicited by vaccination modulating and improving the immunogenicity of the vaccine. Full article
(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)
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28 pages, 4591 KiB  
Review
Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis
by Pascal Roland Enok Bonong, Monica Zahreddine, Chantal Buteau, Michel Duval, Louise Laporte, Jacques Lacroix, Caroline Alfieri and Helen Trottier
Vaccines 2021, 9(3), 288; https://doi.org/10.3390/vaccines9030288 - 19 Mar 2021
Cited by 12 | Viewed by 2690
Abstract
This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to [...] Read more.
This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing. Full article
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15 pages, 2977 KiB  
Article
Perception of COVID-19 Vaccination Amongst Physicians in Colombia
by Jorge L. Alvarado-Socarras, Andrea Liliana Vesga-Varela, Doris Cristina Quintero-Lesmes, Marcela M. Fama-Pereira, Norma C. Serrano-Diaz, Mauricio Vasco, Virgil Carballo-Zarate, Lysien I. Zambrano, Alberto Paniz-Mondolfi and Alfonso J. Rodriguez-Morales
Vaccines 2021, 9(3), 287; https://doi.org/10.3390/vaccines9030287 - 19 Mar 2021
Cited by 27 | Viewed by 9020
Abstract
Introduction: The SARS-CoV-2/COVID-19 pandemic has triggered the need to develop rapidly effective and safe vaccines to prevent infection, particularly in those at-risk populations such as medical personnel. This study’s objective was to assess the perception of COVID-19 vaccination amongst Colombian physicians featuring [...] Read more.
Introduction: The SARS-CoV-2/COVID-19 pandemic has triggered the need to develop rapidly effective and safe vaccines to prevent infection, particularly in those at-risk populations such as medical personnel. This study’s objective was to assess the perception of COVID-19 vaccination amongst Colombian physicians featuring two different scenarios of COVID-19 vaccination. Methods: A cross-sectional analytical study was carried out through an online survey directed at medical staff in several cities in Colombia. The percentage of physicians who have a positive perception to be vaccinated and the associated factors that determine that decision were determined. A binomial regression analysis adjusted for age and sex was carried out, taking as a dependent variable the acceptance of free vaccination with an effectiveness of 60 and 80%. The most significant factors were determined in the non-acceptance of vaccination. Results: Between 77.0% and 90.7% of physicians in Colombia accept COVID-19 vaccination, according to the scenario evaluated where the vaccine’s effectiveness was 60 or 80%, respectively. Medical specialty, having never paid for a vaccine, recommending the administration of the vaccine to their parents or people over 70 years, and dispensing the vaccine to their children, were the factors to consider to be vaccinated for free with an effectiveness of 60% and 80%. Conclusions: There is a high perception of the intention to vaccinate physicians in Colombia against COVID-19, and this is very similar to that of the general population. Full article
(This article belongs to the Special Issue Epidemiology of COVID-19)
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22 pages, 10251 KiB  
Article
A Call for a Reform of the Influenza Immunization Program in Mexico: Epidemiologic and Economic Evidence for Decision Making
by Roberto Tapia-Conyer, Miguel Betancourt-Cravioto, Alejandra Montoya, Jorge Abelardo Falcón-Lezama, Myrna María Alfaro-Cortes and Rodrigo Saucedo-Martínez
Vaccines 2021, 9(3), 286; https://doi.org/10.3390/vaccines9030286 - 19 Mar 2021
Cited by 6 | Viewed by 2681
Abstract
Limited information is available to determine the effectiveness of Mexico’s national influenza vaccination guidelines and inform policy updates. We aim to propose reforms to current influenza vaccination policies based on our analysis of cost-effectiveness studies. This cross-sectional epidemiological study used influenza case, death, [...] Read more.
Limited information is available to determine the effectiveness of Mexico’s national influenza vaccination guidelines and inform policy updates. We aim to propose reforms to current influenza vaccination policies based on our analysis of cost-effectiveness studies. This cross-sectional epidemiological study used influenza case, death, discharge and hospitalization data from several influenza seasons and applied a one-year decision-analytic model to assess cost-effectiveness. The primary health outcome was influenza cases avoided; secondary health outcomes were influenza-related events associated with case reduction. By increasing vaccination coverage to 75% in the population aged 12–49 years with risk factors (diabetes, high blood pressure, morbid obesity, chronic renal failure, asthma, pregnancy), and expanding universal vaccination coverage to school-aged children (5–11 years) and adults aged 50–59 years, 7142–671,461 influenza cases; 1–15 deaths; 7615–262,812 healthcare visits; 2886–154,143 emergency room admissions and 2891–97,637 hospitalizations could be prevented (ranges correspond to separate age and risk factor groups), with a net annual savings of 3.90 to 111.99 million USD. Such changes to the current vaccination policy could potentially result in significant economic and health benefits. These data could be used to inform the revision of a vaccination policy in Mexico with substantial social value. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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17 pages, 1694 KiB  
Article
Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge
by Xinle Cui, Zhouhong Cao, Yuriko Ishikawa, Sara Cui, Ken-Ichi Imadome and Clifford M. Snapper
Vaccines 2021, 9(3), 285; https://doi.org/10.3390/vaccines9030285 - 19 Mar 2021
Cited by 15 | Viewed by 3093
Abstract
Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B [...] Read more.
Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine. Full article
(This article belongs to the Special Issue The Path towards Effective Vaccines for Chronic Viral Infections)
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16 pages, 9803 KiB  
Review
Opportunities for Refinement of Non-Human Primate Vaccine Studies
by Mark J. Prescott, Carolyn Clark, William E. Dowling and Amy C. Shurtleff
Vaccines 2021, 9(3), 284; https://doi.org/10.3390/vaccines9030284 - 19 Mar 2021
Cited by 5 | Viewed by 6749
Abstract
Non-human primates (NHPs) are used extensively in the development of vaccines and therapeutics for human disease. High standards in the design, conduct, and reporting of NHP vaccine studies are crucial for maximizing their scientific value and translation, and for making efficient use of [...] Read more.
Non-human primates (NHPs) are used extensively in the development of vaccines and therapeutics for human disease. High standards in the design, conduct, and reporting of NHP vaccine studies are crucial for maximizing their scientific value and translation, and for making efficient use of precious resources. A key aspect is consideration of the 3Rs principles of replacement, reduction, and refinement. Funders of NHP research are placing increasing emphasis on the 3Rs, helping to ensure such studies are legitimate, ethical, and high-quality. The UK’s National Centre for the 3Rs (NC3Rs) and the Coalition for Epidemic Preparedness Innovations (CEPI) have collaborated on a range of initiatives to support vaccine developers to implement the 3Rs, including hosting an international workshop in 2019. The workshop identified opportunities to refine NHP vaccine studies to minimize harm and improve welfare, which can yield better quality, more reproducible data. Careful animal selection, social housing, extensive environmental enrichment, training for cooperation with husbandry and procedures, provision of supportive care, and implementation of early humane endpoints are features of contemporary good practice that should and can be adopted more widely. The requirement for high-level biocontainment for some pathogens imposes challenges to implementing refinement but these are not insurmountable. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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12 pages, 8624 KiB  
Brief Report
Zika E Glycan Loop Region and Guillain–Barré Syndrome-Related Proteins: A Possible Molecular Mimicry to Be Taken in Account for Vaccine Development
by Grégorie Lebeau, Etienne Frumence, Jonathan Turpin, Floran Begue, Jean-Jacques Hoarau, Gilles Gadea, Pascale Krejbich-Trotot, Philippe Desprès and Wildriss Viranaicken
Vaccines 2021, 9(3), 283; https://doi.org/10.3390/vaccines9030283 - 19 Mar 2021
Cited by 4 | Viewed by 2615
Abstract
The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain–Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific. Here, we hypothesize [...] Read more.
The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain–Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. The analysis of the ZIKV epidemic strains showed that the glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS through a potent mimicry with Heat Shock 70 kDa protein 12A (HSP70 12A). Full article
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10 pages, 1614 KiB  
Article
Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia
by Juan David Ramírez, Marina Muñoz, Nathalia Ballesteros, Luz H. Patiño, Sergio Castañeda, Carlos A. Rincón, Claudia Mendez, Carolina Oliveros, Julie Perez, Elizabeth K. Márquez, Frank de los Santos Ortiz, Camilo A. Correa-Cárdenas, Maria Clara Duque and Alberto Paniz-Mondolfi
Vaccines 2021, 9(3), 282; https://doi.org/10.3390/vaccines9030282 - 19 Mar 2021
Cited by 15 | Viewed by 4774
Abstract
The continuing evolution of SARS-CoV-2 and the emergence of novel variants have raised concerns about possible reinfection events and potential changes in the coronavirus disease 2019 (COVID-19) transmission dynamics. Utilizing Oxford Nanopore technologies, we sequenced paired samples of three patients with positive RT-PCR [...] Read more.
The continuing evolution of SARS-CoV-2 and the emergence of novel variants have raised concerns about possible reinfection events and potential changes in the coronavirus disease 2019 (COVID-19) transmission dynamics. Utilizing Oxford Nanopore technologies, we sequenced paired samples of three patients with positive RT-PCR results in a 1–2-month window period, and subsequent phylogenetics and genetic polymorphism analysis of these genomes was performed. Herein, we report, for the first time, genomic evidence of one case of reinfection in Colombia, exhibiting different SARS-CoV-2 lineage classifications between samples (B.1 and B.1.1.269). Furthermore, we report two cases of possible viral persistence, highlighting the importance of deepening our understanding on the evolutionary intra-host traits of this virus throughout different timeframes of disease progression. These results emphasize the relevance of genomic surveillance as a tool for understanding SARS-CoV-2 infection dynamics, and how this may translate effectively to future control and mitigations efforts, such as the national vaccination program. Full article
(This article belongs to the Special Issue Epidemiology of COVID-19)
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14 pages, 5929 KiB  
Study Protocol
Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics
by Andrea Haekyung Haselbeck, Birkneh Tilahun Tadesse, Juyeon Park, Malick M. Gibani, Ligia María Cruz Espinoza, Ariane Abreu, Craig Van Rensburg, Michael Owusu-Ansah, Sampson Twuamsi-Ankrah, Michael Owusu, Isaac Aguna, Valentina Picot, Hyonjin Jeon, Ellen Higginson, Sunju Park, Zenaida R. Mojares, Justin Im, Megan E. Carey, Farhana Khanam, Susan Tonks, Gordon Dougan, Deokryun Kim, Jonathan Sugimoto, Vittal Mogasale, Kathleen M. Neuzil, Firdausi Qadri, Yaw Adu-Sarkodie, Ellis Owusu-Dabo, John Clemens and Florian Marksadd Show full author list remove Hide full author list
Vaccines 2021, 9(3), 281; https://doi.org/10.3390/vaccines9030281 - 19 Mar 2021
Cited by 4 | Viewed by 6470
Abstract
Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform [...] Read more.
Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392). Full article
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11 pages, 411 KiB  
Article
Disparity of Cervical Cancer Risk in Young Japanese Women: Bipolarized Status of HPV Vaccination and Cancer Screening
by Mariko Taniguchi, Yutaka Ueda, Asami Yagi, Ai Miyoshi, Yusuke Tanaka, Ryoko Minekawa, Masayuki Endo, Takuji Tomimatsu, Kei Hirai, Tomio Nakayama and Tadashi Kimura
Vaccines 2021, 9(3), 280; https://doi.org/10.3390/vaccines9030280 - 19 Mar 2021
Cited by 6 | Viewed by 2278
Abstract
Women born between 1994 and 1999 achieved high vaccination rates for human papillomavirus (HPV); they are now reaching the age of cervical cancer screening programs in Japan. In this study, we aimed to investigate the health awareness of HPV-vaccinated and unvaccinated women and [...] Read more.
Women born between 1994 and 1999 achieved high vaccination rates for human papillomavirus (HPV); they are now reaching the age of cervical cancer screening programs in Japan. In this study, we aimed to investigate the health awareness of HPV-vaccinated and unvaccinated women and to create tailored leaflets recommending cervical cancer screening for each. Surveys on the cancer screening rates for HPV-vaccinated and unvaccinated women aged 20 and 21 have demonstrated that the rate was significantly higher (p < 0.01) in vaccinated (6.2%) than in unvaccinated women (3.1%). Next, interviews and Internet questionnaires clarified that there was a trend that vaccinated women have a better health consciousness than the unvaccinated ones, and that in unvaccinated women, their willingness to receive cervical cancer screening was significantly enhanced by the fear of developing cancer. Finally, in a prospective study, the increase in the screening rate for both vaccinated and unvaccinated groups after they read tailored leaflets, from 6.4% to 7.4% and from 3.9% to 5.1%, respectively, was not statistically significant compared to the groups provided with a standard reminder letter. Cervical cancer control measures might be enhanced by recommending cervical cancer screening in ways better tailored to HPV vaccination status. Full article
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9 pages, 836 KiB  
Article
Fendrix® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B® Vaccination
by Juan José Tejada-Pérez, Juan José Vázquez-Vicente, María Renée Herrera-Burgos, Francisco Gabriel Martín-Martín, Tesifón Parrón-Carreño and Raquel Alarcón-Rodríguez
Vaccines 2021, 9(3), 279; https://doi.org/10.3390/vaccines9030279 - 19 Mar 2021
Cited by 4 | Viewed by 2380
Abstract
Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with [...] Read more.
Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with Engerix B® lowers this risk by providing workers with immunity to the virus. However, through the years, we have encountered nonresponsive health personnel to the Engerix B® vaccine; hence, the Occupational Health Service of Poniente Hospital studied the Fendrix® adjuvanted vaccine as an alternative vaccine to develop immunological responses in healthcare workers who do not respond to vaccination with Engerix B®. In our study, we employed a vaccination schedule with the Fendrix® vaccine, performing serology tests on the cases after the application of each dose. The results obtained showed humoral immunity in 92.3% of the cases, with a remarkable increase in antibody titer after the first doses. These encouraging results support the future inclusion of this vaccine as one possible alternative for the immunization to HBV for healthcare workers nonresponsive to Engerix B®. Full article
(This article belongs to the Special Issue Vaccines against Hepatitis Viruses)
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15 pages, 3342 KiB  
Article
K48-Linked Ubiquitination Contributes to Nicotine-Augmented Bone Marrow-Derived Dendritic-Cell-Mediated Adaptive Immunity
by Chun Fang Hu, Xiao Yan Liao, Dan Dan Xu, Yi Bin Ruan and Feng Guang Gao
Vaccines 2021, 9(3), 278; https://doi.org/10.3390/vaccines9030278 - 19 Mar 2021
Cited by 1 | Viewed by 2460
Abstract
K48-linked ubiquitination determining antigen degradation and the endosomal recruitments of p97 and Sec61 plays vital roles in dendritic cell (DC) cross-presentation. Our previous studies revealed that nicotine treatment increases bone marrow-derived dendritic cell (BM-DC) cross-presentation and promotes BM-DC-based cytotoxic T lymphocyte (CTL) priming. [...] Read more.
K48-linked ubiquitination determining antigen degradation and the endosomal recruitments of p97 and Sec61 plays vital roles in dendritic cell (DC) cross-presentation. Our previous studies revealed that nicotine treatment increases bone marrow-derived dendritic cell (BM-DC) cross-presentation and promotes BM-DC-based cytotoxic T lymphocyte (CTL) priming. But the effect of nicotine on K48-linked ubiquitination and the mechanism of nicotine-increased BM-DC cross-presentation are still uncertain. In this study, we first demonstrated that ex vivo nicotine administration obviously increased K48-linked ubiquitination in BM-DC. Then, we found that K48-linked ubiquitination was essential for nicotine-augmented cross-presentation, BM-DC-based CTL priming, and thereby the superior cytolytic capacity of DC-activated CTL. Importantly, K48-linked ubiquitination was verified to be necessary for nicotine-augmented endosomal recruitments of p97 and Sec61. Importantly, mannose receptor (MR), which is an important antigenic receptor for cross-presentation, was exactly catalyzed with K48-linked ubiquitination by the treatment with nicotine. Thus, these data suggested that K48-linked ubiquitination contributes to the superior adaptive immunity of nicotine-administrated BM-DC. Regulating K48-linked ubiquitination might have therapeutic potential for DC-mediated immune therapy. Full article
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14 pages, 3983 KiB  
Article
Decrease of IL-5 Production by Naive T Cells Cocultured with IL-18-Producing BCG-Pulsed Dendritic Cells from Patients Allergic to House Dust Mite
by Magdalena Kowalewicz-Kulbat, Piotr Szpakowski, Krzysztof T. Krawczyk, Marek L. Kowalski, Slawomir Kosinski, Franck Biet, Wieslawa Rudnicka and Camille Locht
Vaccines 2021, 9(3), 277; https://doi.org/10.3390/vaccines9030277 - 18 Mar 2021
Cited by 4 | Viewed by 1996
Abstract
The only currently available anti-tuberculosis vaccine, Bacillus Calmette–Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to [...] Read more.
The only currently available anti-tuberculosis vaccine, Bacillus Calmette–Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to reduce IL-5 production and bronchoalveolar eosinophilia in mice. However, their ability to decrease the immune polarization of human Th2 cells is not known. Here, we show that BCG and recombinant BCG producing human IL-18 (rBCG-hIL-18) induced the maturation of Der p 1-stimulated monocyte-derived dendritic cells (MD-DCs) from healthy controls and from patients allergic to house dust mites. After incubation with mycobacteria and Der p 1, MD-DCs produced significantly more IL-23 and IP-10 but had no effect on IL-12p70 or IL-10 production compared to Der p 1-pulsed MD-DCs in the absence of mycobacteria. In the presence of Der p 1, BCG- and rBCG-hIL-18-pulsed MD-DCs cocultured with naive, but not with memory T cells from allergic patients, resulted in a decrease in IL-5 production compared to non-pulsed MD-DCs cultured in the presence of Der p 1. BCG, and especially rBCG-hIL-18, may thus be potential therapeutic tools to reduce exacerbated Th2 responses in patients with allergic asthma. Full article
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4 pages, 359 KiB  
Brief Report
Is COVID-19 a Real Incentive for Flu Vaccination? Let the Numbers Speak for Themselves
by Marcello Di Pumpo, Giuseppe Vetrugno, Domenico Pascucci, Elettra Carini, Viria Beccia, Anna Sguera, Maurizio Zega, Marcello Pani, Andrea Cambieri, Mario Cesare Nurchis, Floriana D’Ambrosio, Gianfranco Damiani and Patrizia Laurenti
Vaccines 2021, 9(3), 276; https://doi.org/10.3390/vaccines9030276 - 18 Mar 2021
Cited by 24 | Viewed by 2535
Abstract
Seasonal flu vaccination is one of the most important strategies for preventing influenza. The attitude towards flu vaccination in light of the COVID-19 pandemic has so far been studied in the literature mostly with the help of surveys and questionnaires. Whether a person [...] Read more.
Seasonal flu vaccination is one of the most important strategies for preventing influenza. The attitude towards flu vaccination in light of the COVID-19 pandemic has so far been studied in the literature mostly with the help of surveys and questionnaires. Whether a person chooses to be vaccinated or not during the COVID-19 pandemic, however, speaks louder than any declaration of intention. In our teaching hospital, we registered a statistically significant increase in flu vaccination coverage across all professional categories between the 2019/2020 and the 2020/2021 campaign (24.19% vs. 54.56%, p < 0.0001). A linear regression model, based on data from four previous campaigns, predicted for the 2020/2021 campaign a total flu vaccination coverage of 30.35%. A coverage of 54.46% was, instead, observed, with a statistically significant difference from the predicted value (p < 0.0001). The COVID-19 pandemic can, therefore, be considered as an incentive that significantly and dramatically increased adherence to flu vaccination among our healthcare workers. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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10 pages, 253 KiB  
Article
Exploring the Willingness to Accept SARS-CoV-2 Vaccine in a University Population in Southern Italy, September to November 2020
by Gabriella Di Giuseppe, Concetta Paola Pelullo, Giorgia Della Polla, Maria Pavia and Italo Francesco Angelillo
Vaccines 2021, 9(3), 275; https://doi.org/10.3390/vaccines9030275 - 18 Mar 2021
Cited by 49 | Viewed by 2946
Abstract
Understanding whether members of the university population are willing to receive a future vaccination against COVID-19 and identifying barriers may help public health authorities to develop effective strategies and interventions to contain COVID-19. This cross-sectional study explored the willingness to accept a future [...] Read more.
Understanding whether members of the university population are willing to receive a future vaccination against COVID-19 and identifying barriers may help public health authorities to develop effective strategies and interventions to contain COVID-19. This cross-sectional study explored the willingness to accept a future SARS-CoV-2 vaccine in a university population in Southern Italy. The perceived risk level of developing COVID-19 was 6.5 and it was significantly higher among females, younger subjects, and those who agreed/strongly agreed that COVID-19 is a severe disease. Only 21.4% of respondents were not worried at all regarding the safety of the vaccine. Males, not being married/cohabitant, being a faculty member, those who perceived a lower risk of developing COVID-19, and those who did not need information regarding the vaccination against COVID-19 were significantly more likely to have no concern at all regarding the safety of the vaccine. The vast majority (84.1%) were willing to receive a future vaccine against COVID-19. Almost coherently with predictors of concern on the safety of the vaccine, being male, not being married/cohabitant, being a faculty member, not being concerned at all that COVID-19 vaccination might not be safe, and agreeing that COVID-19 can have serious health consequences were significant predictors of the willingness to receive the vaccine against COVID-19. A considerable proportion of the population had a positive willingness to receive the future COVID-19 vaccine, although some concerns have been expressed regarding the effectiveness and safety and public health activities seem necessary to achieve the rate that can lead to the protection of the community. Full article
7 pages, 237 KiB  
Commentary
A Commentary on Realities of Developing COVID-19 Vaccines Discussed through the Global Health Safety Perspective
by Wedad Saeed Al-Qahtani and Fatmah Ahmed Safhi
Vaccines 2021, 9(3), 274; https://doi.org/10.3390/vaccines9030274 - 18 Mar 2021
Cited by 5 | Viewed by 12545
Abstract
SARS-CoV-2 (or simply COVID-19) remains to be a global pandemic issue affecting millions, thus urging the world’s scientific community to develop efficient vaccine and design adequate measures of disease control. Currently, the most economically viable solution to infections and viruses is vaccination, despite [...] Read more.
SARS-CoV-2 (or simply COVID-19) remains to be a global pandemic issue affecting millions, thus urging the world’s scientific community to develop efficient vaccine and design adequate measures of disease control. Currently, the most economically viable solution to infections and viruses is vaccination, despite the possible concerns about side effects from implementing quickly developed vaccine. The current commentary intends to explain the health and safety related to COVID-19 vaccines via a prism of global health safety. Scientists across the globe, along with companies from both public and private sectors, have predictably arranged cooperative programs to learn about COVID-19, along with taking simultaneous steps on devising vaccine and preparing effective treatments plans. Presently, several clinical trials to approve the efficiency of proposed vaccine solutions have been made successfully. Global health safety concerns on vaccine’s efficiency such as high costs of production, provision of vaccine to developing countries, and its influence on the global economy are addressed. This commentary reflects on current efforts related to the development of vaccine against COVID-19, which currently affects the global health status and economy. In addition, the commentary aims at addressing potential risks related to the development of COVID-19 vaccine from the global health safety perspective. Full article
(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)
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