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Vaccines, Volume 11, Issue 4 (April 2023) – 169 articles

Cover Story (view full-size image): Radioresistance is a major barrier to achieving efficient local tumor control. The combination of radiotherapy (RT) with immunotherapy has improved outcomes for patients with solid tumors. It becomes important to understand how radiation modulates immune mechanisms of radioresistance. We summarize how radiation modulates the expression and activation of Toll-Like Receptors in the tumor microenvironment. Radiation induces the release of damage associated molecular patterns from damaged or dying cells. DAMPs can be recognized by pattern recognition receptors such as TLRs. This triggers a signaling cascade that results in a pro- or anti-tumor effect, depending on the specific TLR and the type of cancer. The rational combination of TLR-based therapies with RT can enhance tumor recognition by antigen-presenting cells and lead to sustained antitumor immunity and effective local tumor control. View this paper
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Article
Protective Efficacy of Multiple Epitope-Based Vaccine against Hyalomma anatolicum, Vector of Theileria annulata and Crimean–Congo Hemorrhagic Fever Virus
Vaccines 2023, 11(4), 881; https://doi.org/10.3390/vaccines11040881 - 21 Apr 2023
Viewed by 959
Abstract
Hyalomma anatolicum is the principal vector for Theileria annulata, T. equi, and T. Lestoquardi in animals and the Crimean–Congo hemorrhagic fever virus in humans. Due to the gradual loss of efficacy of the available acaricides against field tick populations, the development [...] Read more.
Hyalomma anatolicum is the principal vector for Theileria annulata, T. equi, and T. Lestoquardi in animals and the Crimean–Congo hemorrhagic fever virus in humans. Due to the gradual loss of efficacy of the available acaricides against field tick populations, the development of phytoacaricides and vaccines has been considered the two most critical components of the integrated tick management strategies. In the present study, in order to induce both cellular and humoral immune responses in the host against H. anatolicum, two multi-epitopic peptides (MEPs), i.e., VT1 and VT2, were designed. The immune-stimulating potential of the constructs was determined by in silicoinvestigation on allergenicity (non-allergen, antigenic (0.46 and 1.0046)), physicochemical properties (instability index 27.18 and 35.46), as well as the interaction of constructs with TLRs by docking and molecular dynamics analysis. The immunization efficacy of the MEPs mixed with 8% MontanideTM gel 01 PR against H. anatolicum larvae was determined as 93.3% and 96.9% in VT1- and VT2-immunized rabbits, respectively. Against adults, the efficacy was 89.9% and 86.4% in VT1- and VT2-immunized rabbits, respectively. A significant (p < 0.001) reduction in the anti-inflammatory cytokine (IL-4) and significantly higher IgG response was observed in a VT1-immunized group of rabbits as compared with the response observed in the control group. However, in the case of the VT2-immunized rabbits, an elevated anti-VT2 IgG and pro-inflammatory cytokine (IL-2) (>30 fold) along with a decreased level of anti-inflammatory cytokine IL-4 (0.75 times) was noted. The efficacy of MEP and its potential immune stimulatory responses indicate that it might be useful for tick management. Full article
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Systematic Review
Healthcare Workers’ Attitudes towards Mandatory COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Vaccines 2023, 11(4), 880; https://doi.org/10.3390/vaccines11040880 - 21 Apr 2023
Viewed by 1360
Abstract
Background: COVID-19 vaccine mandates are considered a controversial public health policy both in public debate and among healthcare workers (HCWs). Thus, the objective of this systematic review is to give a deep insight into HCWs’ views and attitudes towards COVID-19 vaccination mandates amid [...] Read more.
Background: COVID-19 vaccine mandates are considered a controversial public health policy both in public debate and among healthcare workers (HCWs). Thus, the objective of this systematic review is to give a deep insight into HCWs’ views and attitudes towards COVID-19 vaccination mandates amid the ongoing COVID-19 pandemic. Methods: A systematic literature search of five databases (PubMed, Scopus, Embase, CINAHL, and Web of Science) was conducted between July 2022 and November 2022. Original quantitative studies that addressed the attitudes of HCWs regarding COVID-19 vaccine mandates were considered eligible for this systematic review. All the included studies (n = 57) were critically appraised and assessed for risk of systematic bias. Meta-analyses were performed, providing a pooled estimate of HCWs’ acceptance towards COVID-19 vaccine mandates for: 1. HCWs and 2. the general population. Results: In total, 64% (95% CI: 55%, 72%) of HCWs favored COVID-19 vaccine mandates for HCWs, while 50% (95% CI: 38%, 61%) supported mandating COVID-19 vaccines for the general population. Conclusions: Our findings indicate that mandatory vaccination against COVID-19 is a highly controversial issue among HCWs. The present study provides stakeholders and policy makers with useful evidence related to the compulsory or non-compulsory nature of COVID-19 vaccinations for HCWs and the general population. Other: The protocol used in this review is registered on PROSPERO with the ID number: CRD42022350275. Full article
(This article belongs to the Special Issue Vaccines and Vaccinations in the Pandemic Period)
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Brief Report
Differences in the Expression Levels of SARS-CoV-2 Spike Protein in Cells Treated with mRNA-Based COVID-19 Vaccines: A Study on Vaccines from the Real World
Vaccines 2023, 11(4), 879; https://doi.org/10.3390/vaccines11040879 - 21 Apr 2023
Viewed by 2183
Abstract
Comirnaty (BNT162b2) and Spikevax (mRNA-1273) COVID-19 vaccines encode a full-length SARS-CoV-2 Spike (S) protein. To evaluate whether the S-protein expressed following treatment with the two vaccines differs in the real-world context, two cell lines were treated for 24 h with two concentrations of [...] Read more.
Comirnaty (BNT162b2) and Spikevax (mRNA-1273) COVID-19 vaccines encode a full-length SARS-CoV-2 Spike (S) protein. To evaluate whether the S-protein expressed following treatment with the two vaccines differs in the real-world context, two cell lines were treated for 24 h with two concentrations of each vaccine, and the expression of the S-protein was evaluated using flow cytometry and ELISA. Vaccines were obtained from three vaccination centers in Perugia (Italy) that provided us with residual vaccines present in vials after administration. Interestingly, the S-protein was detected not only on the cell membrane but also in the supernatant. The expression was dose-dependent only in Spikevax-treated cells. Furthermore, the S-protein expression levels in both cells and supernatant were much higher in Spikewax-than in Comirnaty-treated cells. Differences in S-protein expression levels following vaccine treatment may be attributed to variations in the efficacy of lipid nanoparticles, differences in mRNA translation rates and/or loss of some lipid nanoparticles’ properties and mRNA integrity during transport, storage, or dilution, and may contribute to explaining the slight differences in the efficacy and safety observed between the Comirnaty and Spikevax vaccines. Full article
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Article
Knowledge of Community Pharmacists in Saudi Arabia Regarding Human Monkeypox, Its Management, Prevention, and Vaccination: Findings and Implications
Vaccines 2023, 11(4), 878; https://doi.org/10.3390/vaccines11040878 - 21 Apr 2023
Viewed by 1080
Abstract
Many cases of monkeypox have recently been reported in countries where this disease is not endemic, raising a global health concern. Consequently, healthcare professionals (HCPs), including pharmacists, need to be aware of the disease, its prevention, including the role of vaccines, and its [...] Read more.
Many cases of monkeypox have recently been reported in countries where this disease is not endemic, raising a global health concern. Consequently, healthcare professionals (HCPs), including pharmacists, need to be aware of the disease, its prevention, including the role of vaccines, and its management to reduce transmission. A cross-sectional, questionnaire-based study was conducted among conveniently sampled community pharmacists in the Qassim region of Saudi Arabia. A total of 189 community pharmacists participated in the study, giving a response rate of 72.97%. From these, 86.77% were male, 51.32% were ≤30 years old, 36.51% were aged between 31–40 years, and 43.39% had 1–5 years of experience as community pharmacists. Their overall knowledge was 17.72 ± 5.56 out of a maximum of 28. The overall rate of correct answers for the knowledge statements was 63.29%, with 52.4% answering ≥50–<75% of the knowledge questions correctly and 31.2% answering ≥75% of the questions correctly. The knowledge subdomain related to diagnosis and clinical characteristics recorded the highest score, with the subdomain relating to causative pathogens and epidemiology recording a lower score. Overall, community pharmacists had moderate knowledge of monkeypox and its clinical management, prevention, and the role of vaccines, which is a concern for the future. Consequently, tailored, flexible, and timely educational interventions are needed to ensure that HCPs, including community pharmacists, are fully equipped with the latest evidence-based knowledge regarding this viral disease to reduce transmission and improve care. Full article
(This article belongs to the Section Vaccines and Society)
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Article
Innate Immune Response Assessment in Cyprinus carpio L. upon Experimental Administration with Artemia salina Bio-Encapsulated Aeromonas hydrophila Bacterin
Vaccines 2023, 11(4), 877; https://doi.org/10.3390/vaccines11040877 - 21 Apr 2023
Viewed by 700
Abstract
The present study aimed to analyze the enhancement of innate immune responses in juvenile-stage common carp (Cyprinus carpio L.), upon the administration of heat-killed Aeromonas hydrophila at a dosage of 1 × 107 CFU ml−1 through bio-encapsulation in the aquatic [...] Read more.
The present study aimed to analyze the enhancement of innate immune responses in juvenile-stage common carp (Cyprinus carpio L.), upon the administration of heat-killed Aeromonas hydrophila at a dosage of 1 × 107 CFU ml−1 through bio-encapsulation in the aquatic crustacean, Artemia salina. This work emphasizes the modulation of innate immune response when administered with the bio-encapsulated heat-killed antigen that acts as an inactivated vaccine against Motile Aeromonas Septicemia disease. Bio-encapsulated oral administration of antigens promotes innate immunity in juvenile-stage fishes. The optimization of effective bio-encapsulation of bacterin in Artemia salina nauplii was carried out and the best optimal conditions were chosen for immunization. The functional immune parameters such as myeloperoxidase, lysozyme, alkaline phosphatase, antiprotease and respiratory burst activity in serum, blood and intestinal tissue samples were analyzed along with blood differential leukocyte count and tissue histopathology studies. Both humoral and cellular immune responses analyzed were substantially induced or enhanced in the treatment groups in comparison with the control group. The results showed a significant variation in the bio-encapsulation group than the control group and also were comparable to the protection conferred with immersion route immunization under similar conditions. Thus, most of the innate non-specific immune responses are inducible, despite being constitutive of the fish immune system, to exhibit a basal level of protection and a road to better vaccination strategy in Cyprinus carpio L. aquaculture worldwide. Full article
(This article belongs to the Special Issue Fish Viruses and Vaccination)
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Communication
Bolstering the Measurement of Racial Inequity of COVID-19 Vaccine Uptake
Vaccines 2023, 11(4), 876; https://doi.org/10.3390/vaccines11040876 - 21 Apr 2023
Viewed by 577
Abstract
Inequities in COVID-19 vaccine uptake by racialized groups have been persistent throughout the vaccine rollout, leading to disparate burdens of COVID-19 outcomes. A cross-sectional study was conducted to determine COVID-19 vaccine uptake across racialized groups within the nine-county Finger Lakes region of New [...] Read more.
Inequities in COVID-19 vaccine uptake by racialized groups have been persistent throughout the vaccine rollout, leading to disparate burdens of COVID-19 outcomes. A cross-sectional study was conducted to determine COVID-19 vaccine uptake across racialized groups within the nine-county Finger Lakes region of New York State in December 2021. Cross-matching and validation were performed across multiple health information systems for the region to reduce the percentage of vaccine records with missing race information. Additionally, imputation techniques were applied to address the remaining missing values. Uptake of ≥1 dose of the COVID-19 vaccine by race was then examined. By December 2021, 828,551 individuals in our study region had received ≥1 dose of the COVID-19 vaccine, with ~25% having missing race values. Cross-matching and validation within existing records reduced this to ~7%. Uptake of ≥1 dose of a COVID-19 vaccine was greatest among individuals identifying as White, followed by those identifying as Black. The application of imputation techniques reduced the percent of missing race values to <1%; however, this reduction did not significantly change the distribution of vaccine uptake across race groups. Utilization of relevant health information systems, accompanied by imputation techniques, stands to greatly reduce the burden of missing race data within vaccine registries, facilitating accurate targeted interventions to mitigate inequities in COVID-19 vaccination. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Review
Immune Imprinting and Implications for COVID-19
Vaccines 2023, 11(4), 875; https://doi.org/10.3390/vaccines11040875 - 20 Apr 2023
Viewed by 1225
Abstract
Immunological memory is the key source of protective immunity against pathogens. At the current stage of the COVID-19 pandemic, heterologous combinations of exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, the downside of memory, might limit [...] Read more.
Immunological memory is the key source of protective immunity against pathogens. At the current stage of the COVID-19 pandemic, heterologous combinations of exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, the downside of memory, might limit the generation of de novo immune response against variant infection or the response to the next-generation vaccines. Here, we review mechanistic basis of immune imprinting by focusing on B cell immunobiology and discuss the extent to which immune imprinting is harmful, as well as its effect on SARS-CoV-2 infection and vaccination. Full article
(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)
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Article
Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell®
Vaccines 2023, 11(4), 874; https://doi.org/10.3390/vaccines11040874 - 20 Apr 2023
Viewed by 925
Abstract
The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to [...] Read more.
The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4+/CD8+ T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell® thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19. Full article
(This article belongs to the Special Issue Advances in COVID-19 Vaccines Development)
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Systematic Review
Factors Influencing the Intention and Uptake of COVID-19 Vaccines on the African Continent: A Scoping Review
Vaccines 2023, 11(4), 873; https://doi.org/10.3390/vaccines11040873 - 20 Apr 2023
Viewed by 828
Abstract
The COVID-19 pandemic is a severe concern worldwide, particularly in Africa. Vaccines are crucial in the fight against the COVID-19 pandemic. This scoping review examined existing literature from 2020 to 2022 on individual, interpersonal, and structural barriers and facilitators to COVID-19 vaccination within [...] Read more.
The COVID-19 pandemic is a severe concern worldwide, particularly in Africa. Vaccines are crucial in the fight against the COVID-19 pandemic. This scoping review examined existing literature from 2020 to 2022 on individual, interpersonal, and structural barriers and facilitators to COVID-19 vaccination within Africa to facilitate more informed health promotion interventions to improve vaccine uptake. This review was conducted using Arksey and O’Malley’s five-stage methodological framework. A comprehensive search was undertaken from 2021 to 2022 using six electronic databases: EBSCOhost, PubMed, Web of Science, ProQuest, WorldCat Discovery, and Google Scholar. Data was collected, charted into themes, and summarized using a standard data extraction sheet in Microsoft Excel. A total of forty (n = 40) published academic articles were reviewed, with many conducted in Nigeria (n = 10), followed by Ethiopia (n = 5) and Ghana (n = 4) and the rest elsewhere in Africa. Thematic narratives were used to report data into six themes: attitudes and perceptions about COVID-19 vaccines, intention to uptake COVID-19 vaccines; factors and barriers associated with COVID-19 vaccine uptake; socio-demographic determinants affecting the intention and uptake; and information sources for COVID-19 vaccines. The intention for uptake ranged from 25% to 80.9%, resulting in a suboptimal uptake intention rate (54.2%) on the African continent. Factors that promoted vaccine acceptance included confidence in the COVID-19 vaccines and the desire to protect people. Age, education, and gender were the most common factors significantly associated with vaccine acceptance. Most studies revealed that considerable barriers to vaccine uptake exist in Africa. Concerns about potential side effects, vaccine ineffectiveness, a perceived lack of information, and inaccessibility were among the individual, interpersonal, and structural barriers to COVID-19 vaccine uptake. The unwillingness to receive the COVID-19 vaccine was strongly correlated with being female. Mass and social media were the main sources of information regarding COVID-19 vaccines. To encourage vaccine uptake, governments should pay attention to refuting misinformation through integrated community-based approaches, such as creating messages that convey more than just information. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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Article
Using Electronic Reminders to Improve Human Papillomavirus (HPV) Vaccinations among Primary Care Patients
Vaccines 2023, 11(4), 872; https://doi.org/10.3390/vaccines11040872 - 20 Apr 2023
Viewed by 908
Abstract
The COVID-19 pandemic led to delays in routine preventative primary care and declines in HPV immunization rates. Providers and healthcare organizations needed to explore new ways to engage individuals to resume preventive care behaviors. Thus, we evaluated the effectiveness of using customized electronic [...] Read more.
The COVID-19 pandemic led to delays in routine preventative primary care and declines in HPV immunization rates. Providers and healthcare organizations needed to explore new ways to engage individuals to resume preventive care behaviors. Thus, we evaluated the effectiveness of using customized electronic reminders with provider recommendations for HPV vaccination to increase HPV vaccinations among adolescents and young adults, ages 9–25. Using stratified randomization, participants were divided into two groups: usual care (control) (N = 3703) and intervention (N = 3705). The control group received usual care including in-person provider recommendations, visual reminders in exam waiting rooms, bundling of vaccinations, and phone call reminders. The intervention group received usual care and an electronic reminder (SMS, email or patient portal message) at least once, and up to three times (spaced at an interval of 1 reminder per month). The intervention group had a 17% statistically significantly higher odds of uptake of additional HPV vaccinations than the usual care group (Adjusted Odds Ratio: 1.17, 95% CI: 1.01–1.36). This work supports previous findings that electronic reminders are effective at increasing immunizations and potentially decreasing healthcare costs for the treatment of HPV-related cancers. Full article
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Brief Report
SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy
Vaccines 2023, 11(4), 871; https://doi.org/10.3390/vaccines11040871 - 20 Apr 2023
Viewed by 611
Abstract
Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with [...] Read more.
Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy. Full article
(This article belongs to the Special Issue Neutralizing Antibodies against SARS-CoV-2 and HIV)
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Article
Views and Perceptions of People Aged 55+ on the Vaccination Programme for Older Adults in the UK: A Qualitative Study
Vaccines 2023, 11(4), 870; https://doi.org/10.3390/vaccines11040870 - 20 Apr 2023
Viewed by 611
Abstract
Vaccination reduces the risks related to infectious disease, especially among more vulnerable groups, such as older adults. The vaccines available to older adults in the UK through the government-funded programme currently include influenza, pneumococcal, shingles and COVID-19 vaccines. The purpose of the programme [...] Read more.
Vaccination reduces the risks related to infectious disease, especially among more vulnerable groups, such as older adults. The vaccines available to older adults in the UK through the government-funded programme currently include influenza, pneumococcal, shingles and COVID-19 vaccines. The purpose of the programme is disease prevention and improving wellbeing among the ageing population. Yet, the target population’s views of the programme remain unknown. This paper aims to increase the understanding of older adults’ perceptions of the vaccination programme available in the UK. A total of 13 online focus groups (56 informants) were carried out for this qualitative study. The findings indicate that getting vaccinated involves personal decision-making processes, which are influenced by previous experiences and interpersonal interactions. Factors related to the wider community and culture are less prominent in explaining vaccination decisions. However, opportunistic vaccination offers, a lack of information and a lack of opportunities to discuss vaccines, especially with healthcare professionals, are prominent factors. The study provides in-depth data about the rationale behind older adults’ vaccination decisions in the UK. We recommend that the provision of information and opportunities to discuss vaccines and infectious disease be improved to enable older adults’ to make better informed decisions regarding the vaccines available to them. Full article
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Systematic Review
Health Systems Determinants of Delivery and Uptake of Maternal Vaccines in Low- and Middle-Income Countries: A Qualitative Systematic Review
Vaccines 2023, 11(4), 869; https://doi.org/10.3390/vaccines11040869 - 19 Apr 2023
Viewed by 736
Abstract
Maternal vaccination is considered a key component of the antenatal care package for improving maternal and child health. Low- and middle-income countries (LMICs) fall short of global targets to prevent maternal and neonatal deaths, with a disproportionate burden of vaccine-preventable diseases. Strategies towards [...] Read more.
Maternal vaccination is considered a key component of the antenatal care package for improving maternal and child health. Low- and middle-income countries (LMICs) fall short of global targets to prevent maternal and neonatal deaths, with a disproportionate burden of vaccine-preventable diseases. Strategies towards ending preventable maternal mortality necessitate a health systems approach to adequately respond to this burden. This review explores the health systems determinants of delivery and uptake of essential maternal vaccines in LMICs. We conducted a qualitative systematic review of articles on maternal vaccination in LMICs, published between 2009 and 2023 in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Thematic analysis was conducted to identify key themes in the literature, interpreted within a conceptual framing that explores the systems determinants influencing maternal vaccines. Our search yielded 1309 records, of which 54 were included, covering 34 LMICs. Most of the included studies were from South America (28/54) and included pregnant women as the primary study population (34/54). The studies explored influenza (25/54) and tetanus toxoid (20/54) vaccines predominantly. The findings suggest that systems hardware (lack of clear policy guidelines, ineffective cold-chain management, limited reporting and monitoring systems) are barriers to vaccine delivery. Systems software (healthcare provider recommendations, increased trust, higher levels of maternal education) are enablers to maternal vaccine uptake. Findings show that formulation, dissemination and communication of context-specific policies and guidelines on maternal vaccines should be a priority for decision-makers in LMICs. Full article
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Article
Examining the Impact of Key Factors on COVID-19 Vaccination Coverage in India: A PLS-SEM Approach
Vaccines 2023, 11(4), 868; https://doi.org/10.3390/vaccines11040868 - 19 Apr 2023
Viewed by 683
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, numerous factors determined the performance of COVID-19 vaccination coverage. The purpose of this study is to examine the influence of factors such as government stewardship, planning and implementation, and community participation on COVID-19 vaccination coverage. This [...] Read more.
During the coronavirus disease 2019 (COVID-19) pandemic, numerous factors determined the performance of COVID-19 vaccination coverage. The purpose of this study is to examine the influence of factors such as government stewardship, planning and implementation, and community participation on COVID-19 vaccination coverage. This study applied partial least square structured equation modeling (PLS-SEM) by analyzing 187 responses from the stakeholders involved in vaccination programs in four select states of India. This study empirically validates a framework for improving vaccination coverage by confirming the significant impact of planning and implementation on vaccination coverage followed by government stewardship and community participation. Additionally, this study highlights the individual impact of each factor on vaccination coverage. Based on the findings, strategic recommendations were proposed that can be utilized for formulating policy-level actions to facilitate the vaccination program. Full article
(This article belongs to the Special Issue Epidemiology, Vaccination and Public Health)
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Article
Genomic Analysis of Infectious Bursal Disease Virus in Nigeria: Identification of Unique Mutations of Yet Unknown Biological Functions in Both Segments A and B
Vaccines 2023, 11(4), 867; https://doi.org/10.3390/vaccines11040867 - 19 Apr 2023
Viewed by 545
Abstract
Infectious bursal disease (IBD) is a viral poultry disease known worldwide for impacting the economy and food security. The disease is endemic in Nigeria, with reported outbreaks in vaccinated poultry flocks. To gain insight into the dynamics of infectious bursal disease virus (IBDV) [...] Read more.
Infectious bursal disease (IBD) is a viral poultry disease known worldwide for impacting the economy and food security. The disease is endemic in Nigeria, with reported outbreaks in vaccinated poultry flocks. To gain insight into the dynamics of infectious bursal disease virus (IBDV) evolution in Nigeria, near-complete genomes of four IBDVs were evaluated. Amino acid sequences in the hypervariable region of the VP2 revealed conserved markers (222A, 242I, 256I, 294I and 299S) associated with very virulent (vv) IBDV, including the serine-rich heptapeptide motif (SWSASGS). Based on the newly proposed classification for segments A and B, the IBDVs clustered in the A3B5 group (where A3 are IBDVs with vvIBDV-like segment A, and where B5 are from non-vvIBDV-like segment B) form a monophyletic subcluster. Unique amino acid mutations with yet-to-be-determined biological functions have been observed in both segments. Amino acid sequences of the Nigerian IBDVs showed that they are reassortant viruses. Circulation of reassortant IBDVs may be responsible for the vaccination failures observed in the Nigerian poultry population. Close monitoring of changes in the IBDV genome is recommended to nip deleterious changes in the bud through the identification and introduction of the most appropriate vaccine candidates and advocacy/extension programs for properly implementing disease control. Full article
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Article
Dissolving Microneedles Loaded with Nanoparticle Formulation of Respiratory Syncytial Virus Fusion Protein Virus-like Particles (F-VLPs) Elicits Cellular and Humoral Immune Responses
Vaccines 2023, 11(4), 866; https://doi.org/10.3390/vaccines11040866 - 18 Apr 2023
Viewed by 713
Abstract
Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis and pneumonia in children ages five years and below. Recent outbreaks of the virus have proven that RSV remains a severe burden on healthcare services. Thus, a vaccine for RSV is [...] Read more.
Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis and pneumonia in children ages five years and below. Recent outbreaks of the virus have proven that RSV remains a severe burden on healthcare services. Thus, a vaccine for RSV is a need of the hour. Research on novel vaccine delivery systems for infectious diseases such as RSV can pave the road to more vaccine candidates. Among many novel vaccine delivery systems, a combined system with polymeric nanoparticles loaded in dissolving microneedles holds a lot of potential. In this study, the virus-like particles of the RSV fusion protein (F-VLP) were encapsulated in poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). These NPs were then loaded into dissolving microneedles (MNs) composed of hyaluronic acid and trehalose. To test the in vivo immunogenicity of the nanoparticle-loaded microneedles, Swiss Webster mice were immunized with the F-VLP NPs, both with and without adjuvant monophosphoryl lipid A (MPL) NPs loaded in the MN. The mice immunized with the F-VLP NP + MPL NP MN showed high immunoglobulin (IgG and IgG2a) levels both in the serum and lung homogenates. A subsequent analysis of lung homogenates post-RSV challenge revealed high IgA, indicating the generation of a mucosal immune response upon intradermal immunization. A flowcytometry analysis showed high CD8+ and CD4+ expression in the lymph nodes and spleens of the F-VLP NP + MPL NP MN-immunized mice. Thus, our vaccine elicited a robust humoral and cellular immune response in vivo. Therefore, PLGA nanoparticles loaded in dissolving microneedles could be a suitable novel delivery system for RSV vaccines. Full article
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Article
Identification and Evaluation of Novel Antigen Candidates against Salmonella Pullorum Infection Using Reverse Vaccinology
Vaccines 2023, 11(4), 865; https://doi.org/10.3390/vaccines11040865 - 18 Apr 2023
Viewed by 510
Abstract
Pullorum disease, caused by the Salmonella enterica serovar Gallinarum biovar Pullorum, is a highly contagious disease in the poultry industry, leading to significant economic losses in many developing countries. Due to the emergence of multidrug-resistant (MDR) strains, immediate attention is required to prevent their [...] Read more.
Pullorum disease, caused by the Salmonella enterica serovar Gallinarum biovar Pullorum, is a highly contagious disease in the poultry industry, leading to significant economic losses in many developing countries. Due to the emergence of multidrug-resistant (MDR) strains, immediate attention is required to prevent their endemics and global spreading. To mitigate the prevalence of MDR Salmonella Pullorum infections in poultry farms, it is urgent to develop effective vaccines. Reverse vaccinology (RV) is a promising approach using expressed genomic sequences to find new vaccine targets. The present study used the RV approach to identify new antigen candidates against Pullorum disease. Initial epidemiological investigation and virulent assays were conducted to select strain R51 for presentative and general importance. An additional complete genome sequence (4.7 Mb) for R51 was resolved using the Pacbio RS II platform. The proteome of Salmonella Pullorum was analyzed to predict outer membrane and extracellular proteins, and was further selected for evaluating transmembrane domains, protein prevalence, antigenicity, and solubility. Twenty-two high-scored proteins were identified among 4713 proteins, with 18 recombinant proteins successfully expressed and purified. The chick embryo model was used to assess protection efficacy, in which vaccine candidates were injected into 18-day-old chick embryos for in vivo immunogenicity and protective effects. The results showed that the PstS, SinH, LpfB, and SthB vaccine candidates were able to elicit a significant immune response. Particularly, PstS confers a significant protective effect, with a 75% survival rate compared to 31.25% for the PBS control group, confirming that identified antigens can be promising targets against Salmonella Pullorum infection. Thus, we offer RV to discover novel effective antigens in an important veterinary infectious agent with high priority. Full article
(This article belongs to the Special Issue Vaccines for Chicken)
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Article
Combination of Recombinant Proteins S1/N and RBD/N as Potential Vaccine Candidates
Vaccines 2023, 11(4), 864; https://doi.org/10.3390/vaccines11040864 - 18 Apr 2023
Viewed by 792
Abstract
Despite all successful efforts to develop a COVID-19 vaccine, the need to evaluate alternative antigens to produce next-generation vaccines is imperative to target emerging variants. Thus, the second generation of COVID-19 vaccines employ more than one antigen from severe acute respiratory syndrome coronavirus [...] Read more.
Despite all successful efforts to develop a COVID-19 vaccine, the need to evaluate alternative antigens to produce next-generation vaccines is imperative to target emerging variants. Thus, the second generation of COVID-19 vaccines employ more than one antigen from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce an effective and lasting immune response. Here, we analyzed the combination of two SARS-CoV-2 viral antigens that could elicit a more durable immune response in both T- and B-cells. The nucleocapsid (N) protein, Spike protein S1 domain, and receptor binding domain (RBD) of the SARS-CoV-2 spike surface glycoproteins were expressed and purified in a mammalian expression system, taking into consideration the posttranscriptional modifications and structural characteristics. The immunogenicity of these combined proteins was evaluated in a murine model. Immunization combining S1 or RBD with the N protein induced higher levels of IgG antibodies, increased the percentage of neutralization, and elevated the production of cytokines TNF-α, IFN-γ, and IL-2 compared to the administration of a single antigen. Furthermore, sera from immunized mice recognized alpha and beta variants of SARS-CoV-2, which supports ongoing clinical results on partial protection in vaccinated populations, despite mutations. This study identifies potential antigens for second-generation COVID-19 vaccines. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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Systematic Review
Effectiveness, Immunogenicity and Harms of Additional SARS-CoV-2 Vaccine Doses in Kidney Transplant Recipients: A Systematic Review
Vaccines 2023, 11(4), 863; https://doi.org/10.3390/vaccines11040863 - 18 Apr 2023
Viewed by 666
Abstract
Background: Kidney transplant recipients (KTRs) who have a highly impaired immune response are in need of intensified and safe vaccination strategies to achieve seroconversion and prevent severe disease. Methods: We searched the Web of Science Core Collection, the Cochrane COVID-19 Study Register and [...] Read more.
Background: Kidney transplant recipients (KTRs) who have a highly impaired immune response are in need of intensified and safe vaccination strategies to achieve seroconversion and prevent severe disease. Methods: We searched the Web of Science Core Collection, the Cochrane COVID-19 Study Register and the WHO COVID-19 global literature on coronavirus disease from January 2020 to 22 July 2022 for prospective studies that assessed immunogenicity and efficacy after three or more SARS-CoV-2 vaccine doses. Results: In 37 studies on 3429 patients, de novo seroconversion after three and four vaccine doses ranged from 32 to 60% and 25 to 37%. Variant-specific neutralization was 59 to 70% for Delta and 12 to 52% for Omicron. Severe disease after infection was rarely reported but all concerned KTRs lacked immune responses after vaccination. Studies investigating the clinical course of COVID-19 found remarkably higher rates of severe disease than in the general population. Serious adverse events and acute graft rejections were very rare. Substantial heterogeneity between the studies limited their comparability and summary. Conclusion: Additional SARS-CoV-2 vaccine doses are potent and safe in general terms as well as regarding transplant-specific outcomes whilst the Omicron wave remains a significant threat to KTRs without adequate immune responses. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Brief Report
Safety and Immunogenicity of Enterovirus 71 Vaccine (Vero Cell) Administered Simultaneously with Trivalent Split-Virion Influenza Vaccine in Infants Aged 6–7 Months: A Phase 4, Randomized, Controlled Trial
Vaccines 2023, 11(4), 862; https://doi.org/10.3390/vaccines11040862 - 18 Apr 2023
Viewed by 468
Abstract
Objective: To assess the immunogenicity and safety of the enterovirus 71 vaccine (Vero cell) (EV71 vaccine) and trivalent split-virion influenza vaccine (IIV3). Methods: Healthy infants aged 6–7 months were recruited from Zhejiang Province, Henan Province, and Guizhou Province and randomly assigned [...] Read more.
Objective: To assess the immunogenicity and safety of the enterovirus 71 vaccine (Vero cell) (EV71 vaccine) and trivalent split-virion influenza vaccine (IIV3). Methods: Healthy infants aged 6–7 months were recruited from Zhejiang Province, Henan Province, and Guizhou Province and randomly assigned to the simultaneous vaccination group, EV71 group, and IIV3 group at a ratio of 1:1:1. Then, 3 mL blood samples were collected before vaccination and 28 days after the second dose of vaccine. Cytopathic effect inhibition assay was used to detect EV71 neutralization antibody, and cytopathic effect inhibition assay was used to detect influenza virus antibody. Results: A total of 378 infants were enrolled and received the first dose of vaccine and were included in the safety analysis, and 350 infants were involved in the immunogenicity analysis. The adverse events rates were 31.75%, 28.57%, and 34.13% in the simultaneous vaccination group, EV71 group, and IIV3 group (p > 0.05), respectively. No vaccine-related serious adverse events were reported. After two doses of EV71 vaccine, the seroconversion rates of EV71 neutralizing antibody were 98.26% and 97.37% in the simultaneous vaccination group and the EV71 group, respectively. After two doses of IIV3, the simultaneous vaccination group and the IIV3 group, respectively, had seroconversion rates of 80.00% and 86.78% for H1N1 antibody, 99.13% and 98.35% for H3N2 antibody, and 76.52% and 80.99% for B antibody. There was no statistically significant difference in the seroconversion rates of influenza virus antibodies between groups (p > 0.05). Conclusions: The coadministration of EV71 vaccine and IIV3 has good safety and immunogenicity in infants aged 6–7 months. Full article
(This article belongs to the Special Issue Development and Challenges of Respiratory Disease Vaccines)
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Article
Clinical Characteristics and Outcomes among Vaccinated and Unvaccinated Patients with Cardiovascular Disease Who Were Hospitalized for COVID-19 in Brazil: Retrospective Cohort
Vaccines 2023, 11(4), 861; https://doi.org/10.3390/vaccines11040861 - 18 Apr 2023
Viewed by 691
Abstract
Introduction: COVID-19 in Brazil has already caused, and it still causes, several impacts on health, economy, and education. The risk factors for death involved those with cardiovascular diseases (CVD), which were prioritized for the vaccination of COVID-19. Objective: To investigate the clinical characteristics [...] Read more.
Introduction: COVID-19 in Brazil has already caused, and it still causes, several impacts on health, economy, and education. The risk factors for death involved those with cardiovascular diseases (CVD), which were prioritized for the vaccination of COVID-19. Objective: To investigate the clinical characteristics and outcomes between vaccinated and unvaccinated patients with cardiovascular diseases hospitalized for COVID-19 in Brazil in the year 2022. Methods: A retrospective cohort was analyzed from the year 2022, with cases being hospitalized by COVID-19 being drawn from SIVEP-GRIPE surveillance. We compared clinical characteristics, comorbidities, and outcomes between CVD carriers and non-carriers, and we also compared vaccinated with two doses vs. those that are unvaccinated in CVD carriers. We performed chi-square, odds ratio, logistic regression, and survival analysis. Results: We included, in the cohort, 112,459 hospital inpatients. An amount of 71,661 (63.72%) of the hospitalized patients had CVD. Regarding deaths, 37,888 (33.69%) died. Regarding vaccination against COVID-19, 20,855 (18.54%) people were not vaccinated with any dose among those with CVD. Death p- < 0.001 (OR 1.307-CI 1.235–1.383) and fever p- < 0.001 (OR 1.156-CI 1.098–1.218) were associated with the unvaccinated CVD carriers, and diarrhea p-0.015 (OR 1.116-CI 1.022–1.218), dyspnea p-0.022 (OR 1.074-CI 1.011–1.142), and respiratory distress p-0.021 (OR 1.070-CI 1.011–1.134) were also recorded. Those patients who possessed predictors of death, including invasive ventilation (p- < 0.001 (OR 8.816-CI 8.313–9.350)), were admitted to the ICU p- < 0.001 (OR 1.754-CI 1.684–1.827), and some had respiratory distress p- < 0.001 (OR 1.367-CI 1.312–1.423), dyspnea p < 0.001 (OR 1.341-CI 1.284–1.400), O2 saturation < 95% p- < 0. 001 (OR 1.307-CI 1.254–1.363), they were unvaccinated against COVID-19 p- < 0.001 (OR 1.258-CI 1.200–1.319), they were of male sex p- < 0.001 (OR 1.179-CI 1.138–1.221), they had diarrhea p-0.018 (OR 1.081-CI 1.013–1.154), and they may have been old p < 0.001 (OR 1.034-CI 1.033–1.035). Survival was shorter for the unvaccinated p-0.003, and p- <0.001. Conclusions: We highlight the predictors of death for those unvaccinated against COVID-19 in this research, and we evidenced the benefits of the COVID-19 vaccine in reducing deaths in hospitalized CVD patients. Full article
(This article belongs to the Special Issue Cardiovascular Disease and COVID-19)
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Article
Longitudinal Changes in IgG-Type SARS-CoV-2 Antibody Titers after COVID-19 Vaccination and a Prominent Increase in Antibody Titers When Infected after Vaccination
Vaccines 2023, 11(4), 860; https://doi.org/10.3390/vaccines11040860 - 17 Apr 2023
Cited by 1 | Viewed by 664
Abstract
Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers level and duration of elevated levels are considered important indicators for confirming the efficacy of coronavirus disease 2019 (COVID-19) vaccines. The objective of this study was to demonstrate the changes in antibody titers [...] Read more.
Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers level and duration of elevated levels are considered important indicators for confirming the efficacy of coronavirus disease 2019 (COVID-19) vaccines. The objective of this study was to demonstrate the changes in antibody titers after the second and third doses of the COVID-19 vaccine, and to determine the antibody titers in cases of spontaneous infection with SARS-CoV-2 after vaccination. Materials and Methods: From June 2021 to February 2023, IgG-type SARS-CoV-2 antibody titers were measured in 127 participants, including 74 outpatients and 53 members of staff, at the Osaka Dental University Hospital (64 males and 63 females, mean age 52.3 ± 19.0 years). Results: Consistent with previous reports, the SARS-CoV-2 antibody titer decreased with time, not only after the second dose but also after the third dose of the vaccine if there was no spontaneous COVID-19 infection. We also confirmed that the third booster vaccination was effective in increasing the antibody titer. A total of 21 cases of natural infections were observed after administering two or more doses of the vaccine. Thirteen of these patients had post-infection antibody titers exceeding 40,000 AU/mL, and some cases continued to maintain antibody titers in the tens of thousands of AU/mL even after more than 6 months had passed since infection. Conclusions: The rise in and duration of antibody titers against SARS-CoV-2 are considered important indicators for confirming the efficacy of novel COVID-19 vaccines. A longitudinal follow-up of antibody titers after vaccination in larger studies is warranted. Full article
(This article belongs to the Special Issue Vaccines for COVID-19)
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Article
The Impact of a Revised National Childhood Immunization Schedule on Vaccination Defaulters
Vaccines 2023, 11(4), 859; https://doi.org/10.3390/vaccines11040859 - 17 Apr 2023
Viewed by 601
Abstract
Immunization schedules affect community vaccine uptake rates, especially in children who have defaulted on their regular immunization timelines. In 2020, Singapore revised its National Childhood Immunization Schedule (NCIS) to incorporate two new combination vaccines: the hexavalent hepatitis, diphtheria, acellular pertussis, tetanus (DTaP), hemophilus [...] Read more.
Immunization schedules affect community vaccine uptake rates, especially in children who have defaulted on their regular immunization timelines. In 2020, Singapore revised its National Childhood Immunization Schedule (NCIS) to incorporate two new combination vaccines: the hexavalent hepatitis, diphtheria, acellular pertussis, tetanus (DTaP), hemophilus influenzae b (Hib), inactivated poliovirus (IPV) (6-in-1), and the quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccines, thus reducing the mean number of clinic visits and vaccine doses by two. Our database study aims to evaluate the impact of the 2020 NCIS on catch-up vaccination uptake rates in children at 18 and 24 months of age and the catch-up immunization rates of individual vaccines at two years. Vaccination data from two cohorts, in 2018 (n = 11,371) and in 2019 (n = 11,719), were extracted from the Electronic Medical Records. Catch-up vaccination rates increased by 5.2% and 2.6% in children on the new NCIS at 18 and 24 months, respectively. The uptake of individual 5-in-1 (DTaP, IPV, Hib), MMR, and pneumococcal vaccines increased by 3.7%, 4.1%, and 1.9% at 18 months. Reduced vaccination doses and visits in the new NCIS bring direct and indirect benefits to parents and promote vaccination adherence for their children. These findings highlight the importance of timelines in improving catch-up vaccination rates in any NCIS. Full article
(This article belongs to the Special Issue Vaccines Uptakes and Public Health)
Article
COVID-19 Vaccine Acceptance and Hesitancy in Health Care Workers in Somalia: Findings from a Fragile Country with No Previous Experience of Mass Adult Immunization
Vaccines 2023, 11(4), 858; https://doi.org/10.3390/vaccines11040858 - 17 Apr 2023
Viewed by 634
Abstract
Coverage of COVID-19 vaccines in Somalia remains low, including among health workers. This study aimed to identify factors associated with COVID-19 vaccine hesitancy among health workers. In this cross-sectional, questionnaire-based study, 1476 health workers in government and private health facilities in Somalia’s federal [...] Read more.
Coverage of COVID-19 vaccines in Somalia remains low, including among health workers. This study aimed to identify factors associated with COVID-19 vaccine hesitancy among health workers. In this cross-sectional, questionnaire-based study, 1476 health workers in government and private health facilities in Somalia’s federal member states were interviewed face-to-face about their perceptions of and attitudes toward COVID-19 vaccines. Both vaccinated and unvaccinated health workers were included. Factors associated with vaccine hesitancy were evaluated in a multivariable logistic regression analysis. Participants were evenly distributed by sex, and their mean age was 34 (standard deviation 11.8) years. The overall prevalence of vaccine hesitancy was 38.2%. Of the 564 unvaccinated participants, 39.0% remained hesitant. The factors associated with vaccine hesitancy were: being a primary health care worker (adjusted odds ratio (aOR) = 2.37, 95% confidence interval (CI): 1.15–4.90) or a nurse (aOR = 2.12, 95% CI: 1.05–4.25); having a master’s degree (aOR = 5.32, 95% CI: 1.28–22.23); living in Hirshabelle State (aOR = 3.23, 95% CI: 1.68–6.20); not having had COVID-19 (aOR = 1.96, 95% CI: 1.15–3.32); and having received no training on COVID-19 (aOR = 1.54, 95% CI: 1.02–2.32). Despite the availability of COVID-19 vaccines in Somalia, a large proportion of unvaccinated health workers remain hesitant about being vaccinated, potentially influencing the public’s willingness to take the vaccine. This study provides vital information to inform future vaccination strategies to achieve optimal coverage. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Article
Assessing the Impact of Vaccination on the Dynamics of COVID-19 in Africa: A Mathematical Modeling Study
Vaccines 2023, 11(4), 857; https://doi.org/10.3390/vaccines11040857 - 17 Apr 2023
Viewed by 655
Abstract
Several effective COVID-19 vaccines are administered to combat the COVID-19 pandemic globally. In most African countries, there is a comparatively limited deployment of vaccination programs. In this work, we develop a mathematical compartmental model to assess the impact of vaccination programs on curtailing [...] Read more.
Several effective COVID-19 vaccines are administered to combat the COVID-19 pandemic globally. In most African countries, there is a comparatively limited deployment of vaccination programs. In this work, we develop a mathematical compartmental model to assess the impact of vaccination programs on curtailing the burden of COVID-19 in eight African countries considering SARS-CoV-2 cumulative case data for each country for the third wave of the COVID-19 pandemic. The model stratifies the total population into two subgroups based on individual vaccination status. We use the detection and death rates ratios between vaccinated and unvaccinated individuals to quantify the vaccine’s effectiveness in reducing new COVID-19 infections and death, respectively. Additionally, we perform a numerical sensitivity analysis to assess the combined impact of vaccination and reduction in the SARS-CoV-2 transmission due to control measures on the control reproduction number (Rc). Our results reveal that on average, at least 60% of the population in each considered African country should be vaccinated to curtail the pandemic (lower the Rc below one). Moreover, lower values of Rc are possible even when there is a low (10%) or moderate (30%) reduction in the SARS-CoV-2 transmission rate due to NPIs. Combining vaccination programs with various levels of reduction in the transmission rate due to NPI aids in curtailing the pandemic. Additionally, this study shows that vaccination significantly reduces the severity of the disease and death rates despite low efficacy against COVID-19 infections. The African governments need to design vaccination strategies that increase vaccine uptake, such as an incentive-based approach. Full article
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Article
PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays
Vaccines 2023, 11(4), 856; https://doi.org/10.3390/vaccines11040856 - 17 Apr 2023
Viewed by 604
Abstract
Background: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but a preventive vaccine against LTBI is lacking. Methods: In this study, dominant helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), and B-cell epitopes were identified from nine antigens related [...] Read more.
Background: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but a preventive vaccine against LTBI is lacking. Methods: In this study, dominant helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), and B-cell epitopes were identified from nine antigens related to LTBI and regions of difference (RDs). These epitopes were used to construct a novel multiepitope vaccine (MEV) based on their antigenicity, immunogenicity, sensitization, and toxicity. The immunological characteristics of the MEV were analyzed with immunoinformatics technology and verified by enzyme-linked immunospot assay and Th1/Th2/Th17 cytokine assay in vitro. Results: A novel MEV, designated PP19128R, containing 19 HTL epitopes, 12 CTL epitopes, 8 B-cell epitopes, toll-like receptor (TLR) agonists, and helper peptides, was successfully constructed. Bioinformatics analysis showed that the antigenicity, immunogenicity, and solubility of PP19128R were 0.8067, 9.29811, and 0.900675, respectively. The global population coverage of PP19128R in HLA class I and II alleles reached 82.24% and 93.71%, respectively. The binding energies of the PP19128R-TLR2 and PP19128R-TLR4 complexes were −1324.77 kcal/mol and −1278 kcal/mol, respectively. In vitro experiments showed that the PP19128R vaccine significantly increased the number of interferon gamma-positive (IFN-γ+) T lymphocytes and the levels of cytokines, such as IFN-γ, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10. Furthermore, positive correlations were observed between PP19128R-specific cytokines in ATB patients and individuals with LTBI. Conclusions: The PP19128R vaccine is a promising MEV with excellent antigenicity and immunogenicity and no toxicity or sensitization that can induce robust immune responses in silico and in vitro. This study provides a vaccine candidate for the prevention of LTBI in the future. Full article
(This article belongs to the Special Issue Research Progress of New Tuberculosis Vaccines and Vaccine Design)
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Article
BCG-Vaccinated Children with Contact to Tuberculosis Patients Show Delayed Conversion of Mycobacterium tuberculosis-Specific IFN-γ Release
Vaccines 2023, 11(4), 855; https://doi.org/10.3390/vaccines11040855 - 17 Apr 2023
Viewed by 754
Abstract
Mycobacterium (M.) bovis BCG vaccination is recommended for healthy babies after birth in several countries with a high prevalence of tuberculosis, including Ghana. Previous studies showed that BCG vaccination prevents individuals from developing severe clinical manifestations of tuberculosis, but BCG vaccination effects on [...] Read more.
Mycobacterium (M.) bovis BCG vaccination is recommended for healthy babies after birth in several countries with a high prevalence of tuberculosis, including Ghana. Previous studies showed that BCG vaccination prevents individuals from developing severe clinical manifestations of tuberculosis, but BCG vaccination effects on the induction of IFN-γ after M. tuberculosis infection have hardly been investigated. Here, we performed IFN-γ-based T-cell assays (i.e., IFN-γ Release Assay, IGRA; T-cell activation and maturation marker assay, TAM-TB) in children who had contact with index tuberculosis patients (contacts). These contacts were classified as either being BCG vaccinated at birth (n = 77) or non-BCG-vaccinated (n = 17) and were followed up at three timepoints for a period of one year to determine immune conversion after M. tuberculosis exposure and potential infection. At baseline and month 3, BCG-vaccinated contacts had significantly lower IFN-γ levels after stimulation with M. tuberculosis-specific proteins as compared to non-BCG-vaccinated contacts. This resulted in decreased proportions of positive IGRA results (BCG-vaccinated: 60% at baseline, 57% at month 3; non-BCG-vaccinated: 77% and 88%, respectively) at month 3. However, until month 12, immune conversion in BCG-vaccinated contacts led to balanced proportions in IGRA responders and IFN-γ expression between the study groups. TAM-TB assay analyses confirmed higher proportions of IFN-γ-positive T-cells in non-BCG-vaccinated contacts. Low proportions of CD38-positive M. tuberculosis-specific T-cells were only detected in non-BCG-vaccinated contacts at baseline. These results suggest that BCG vaccination causes delayed immune conversion as well as differences in the phenotype of M. tuberculosis-specific T-cells in BCG-vaccinated contacts of tuberculosis patients. These differences are immune biomarker candidates for protection against the development of severe clinical tuberculosis manifestations. Full article
(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)
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Brief Report
T-ALL Cells as Tool Cells for CAR T Therapy
Vaccines 2023, 11(4), 854; https://doi.org/10.3390/vaccines11040854 - 17 Apr 2023
Viewed by 742
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in [...] Read more.
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T cell malignancies, especially in T-ALL. The main reason for CAR T therapy limitations is that T-ALL cells and normal T cells share antigens, which improves the difficulty of sorting pure T cells, resulting in product contamination, and would lead to CAR T cell fratricide. Thus, we considered creating a CAR on T-ALL tumor cells (CAR T-ALL) to prevent fratricide and eliminate tumor cells. We found that T-ALL cells transduced with CAR would actually commit fratricide. However, CAR T-ALL could kill only tumor cells on T-ALL cell lines, and other types of tumor cells had no killing function after being transferred with CAR. Furthermore, we created CD99 CAR with expression controlled by the Tet-On system on Jurkat cells, which could avoid the fratricide of CAR T-ALL during proliferation, ensuring the controllability of the killing time and effect. Jurkat transduced with a CAR-targeting antigen, which was expressed on other cancer cells, could kill other cancer cell lines, demonstrating that T-ALL cells could be used as tool cells for cancer therapy. Our study supplied a new feasible treatment regimen for cancer treatment in the clinic. Full article
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Article
Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2
Vaccines 2023, 11(4), 853; https://doi.org/10.3390/vaccines11040853 - 16 Apr 2023
Viewed by 5028
Abstract
The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here, [...] Read more.
The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here, we examined that proposition using stochastic computational models of viral transmission and mutation. Specifically, we looked at the likelihood of emergence of immune escape variants requiring multiple mutations and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains, if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured. Full article
(This article belongs to the Special Issue Advances in Vaccinal Control of COVID-19)
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Article
Multicentric Observational Study on Safety and Tolerability of COVID-19 Vaccines in Patients with Angioedema with C1 Inhibitor Deficiency: Data from Italian Network on Hereditary and Acquired Angioedema (ITACA)
Vaccines 2023, 11(4), 852; https://doi.org/10.3390/vaccines11040852 - 16 Apr 2023
Viewed by 707
Abstract
Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data [...] Read more.
Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies. Full article
(This article belongs to the Special Issue Current Understanding of Immune Response after COVID-19 Vaccination)
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