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8 pages, 871 KiB

Open AccessArticle

Epidemiologic Profile of Type-Specific Human Papillomavirus Infection after Initiation of HPV Vaccination

by Masayuki Sekine, Manako Yamaguchi, Risa Kudo, Sharon J. B. Hanley, Megumi Hara, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Sayaka Ikeda, Asami Yagi and Takayuki Enomoto

Vaccines 2020, 8(3), 425; https://doi.org/10.3390/vaccines8030425 - 29 Jul 2020

Cited by 8 | Viewed by 3667

Abstract

Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12–16 years who were born in 1994 or later. The rate of OHPV coverage was 70–80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We [...] Read more.

Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12–16 years who were born in 1994 or later. The rate of OHPV coverage was 70–80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We aim to investigate the change in prevalence of HPV infection after the initiation of HPV vaccination. We recruited females aged 20–21 years attending public cervical cancer screening from 2014 to 2017 fiscal years (April 2014 to March 2018). Residual Pap test specimens were collected for HPV testing. We compared the prevalence of HPV type-specific infection between women registered in 2014 (born in 1993–1994, including the pre-OHPV generation) and registered in 2015–2017 (born in 1994–1997, the OHPV generation). We collected 2379 specimens. The vaccination coverage figures were 30.7%, 86.6%, 88.4% and 93.7% (p < 0.01) from 2014 to 2017, respectively. The prevalence of HPV16/18 infection significantly decreased from 1.3% in 2014 to 0% in 2017 (p = 0.02). The three most prevalent types were HPV52, 16 and 56 in 2014, and HPV52, 58 and 56 in 2015–2017, respectively. HPV16 and 33 infection rates decreased. On the other hand, the HPV58 infection rate was obviously increased after OHPV from 0.3% to 2.1%. Our study demonstrates that the prevalence of HPV16/18 infection dramatically decreased and the profile of type-specific HPV infection was changed after OHPV. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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15 pages, 1879 KiB

Open AccessArticle

Potential and Limitations of Cross-Protective Vaccine against Malaria by Blood-Stage Naturally Attenuated Parasite

by Takashi Imai, Kazutomo Suzue, Ha Ngo-Thanh, Chikako Shimokawa and Hajime Hisaeda

Vaccines 2020, 8(3), 375; https://doi.org/10.3390/vaccines8030375 - 11 Jul 2020

Cited by 4 | Viewed by 3069

Abstract

Human malaria vaccine trials have revealed vaccine efficacy but improvement is still needed. In this study, we aimed to re-evaluate vaccination with blood-stage naturally attenuated parasites, as a whole-organism vaccine model against cross-strain and cross-species malaria, to establish a better vaccination strategy. C57BL/6 [...] Read more.

Human malaria vaccine trials have revealed vaccine efficacy but improvement is still needed. In this study, we aimed to re-evaluate vaccination with blood-stage naturally attenuated parasites, as a whole-organism vaccine model against cross-strain and cross-species malaria, to establish a better vaccination strategy. C57BL/6 mice controlled blood-stage Plasmodium yoelii 17XNL (PyNL) within 1 month of infection, while mice with a variety of immunodeficiencies demonstrated different susceptibilities to PyNL, including succumbing to hyperparasitemia. However, after recovery, survivors had complete protection against a challenge with the lethal strain PyL. Unlike cross-strain protection, PyNL-recovered mice failed to induce sterile immunity against Plasmodium berghei ANKA, although prolonged survival was observed in some vaccinated mice. Splenomegaly is a typical characteristic of malaria; the splenic structure became reorganized to prioritize extra-medullary hematopoiesis and to eliminate parasites. We also found that the peritoneal lymph node was enlarged, containing activated/memory phenotype cells that did not confer protection against PyL challenge. Hemozoins remained in the spleen several months after PyNL infection. Generation of an attenuated human blood-stage parasite expressing proteins from multiple species of malaria would greatly improve anti-malaria vaccination. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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10 pages, 916 KiB

Open AccessArticle

Cross-Reactivity Antibody Response after Vaccination with Modified Live and Killed Bovine Viral Diarrhoea Virus (BVD) Vaccines

by Enrica Sozzi, Cecilia Righi, Massimo Boldini, Moira Bazzucchi, Giulia Pezzoni, Matteo Gradassi, Stefano Petrini, Davide Lelli, Giordano Ventura, Ilaria Pierini, Ana Moreno, Emiliana Brocchi, Antonio Lavazza and Gian Mario De Mia

Vaccines 2020, 8(3), 374; https://doi.org/10.3390/vaccines8030374 - 11 Jul 2020

Cited by 20 | Viewed by 3748

Abstract

Pestivirus A or bovine viral diarrhoea virus (BVDV) type 1 is responsible for cosmopolitan diseases affecting cattle and other ruminants, presenting a wide range of clinical manifestations, with relevant impact on zootechnic production. The objective of the present study was to verify whether [...] Read more.

Pestivirus A or bovine viral diarrhoea virus (BVDV) type 1 is responsible for cosmopolitan diseases affecting cattle and other ruminants, presenting a wide range of clinical manifestations, with relevant impact on zootechnic production. The objective of the present study was to verify whether animals immunised with four commercial vaccines also developed a protective humoral immunity against other viral subgenotypes than those contained in each vaccine. Four groups of 25 bovines each were formed and vaccinated according to the manufacturer’s instructions of the commercial vaccines. On sera collected 28 days after the last vaccination, virus neutralisation tests (VNT) were performed using homologous and heterologous viruses and enzyme-linked immunosorbent assay (ELISA) methods. Finally, the VNT results were comparatively evaluated through a statistical analysis. Serological results highlighted that, although with a different degree of efficiency, the four vaccines resulted in not developing a solid antibody-mediated cross-immunity against all the strains used. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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21 pages, 3157 KiB

Open AccessArticle

Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

by Sergio Utrilla-Trigo, Luis Jiménez-Cabello, Ruymán Alonso-Ravelo, Eva Calvo-Pinilla, Alejandro Marín-López, Sandra Moreno, Gema Lorenzo, Julio Benavides, Sarah Gilbert, Aitor Nogales and Javier Ortego

Vaccines 2020, 8(3), 346; https://doi.org/10.3390/vaccines8030346 - 29 Jun 2020

Cited by 15 | Viewed by 4246

Abstract

The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have [...] Read more.

The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have engineered multiserotype BTV vaccine candidates based on recombinant chimpanzee adenovirus (ChAdOx1) and modified vaccinia virus Ankara (MVA) vectors expressing the NS1 protein of BTV-4 or its truncated form NS1-Nt. A single dose of ChAdOx1-NS1 or ChAdOx1-NS1-Nt induced a moderate CD8+ T cell response and protected IFNAR(-/-) mice against a lethal dose of BTV-4/MOR09, a reassortant strain between BTV-1 and BTV-4, although the animals showed low viremia after infection. Furthermore, IFNAR(-/-) mice immunized with a single dose of ChAdOx1-NS1 were protected after challenge with a lethal dose of BTV-8 in absence of viremia nor clinical signs. Additionally, the heterologous prime-boost ChAdOx1/MVA expressing NS1 or NS1-Nt elicited a robust NS1 specific CD8+ T cell response and protected the animals against BTV-4/MOR09 even 16 weeks after immunization, with undetectable levels of viremia at any time after challenge. Subsequently, the best immunization strategy based on ChAdOx1/MVA-NS1 was assayed in sheep. Non-immunized animals presented fever and viremia levels up to 10⁴ PFU/mL after infection. In contrast, although viremia was detected in immunized sheep, the level of virus in blood was 100 times lower than in non-immunized animals in absence of clinical signs. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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19 pages, 2291 KiB

Open AccessArticle

Limited Cross-Protection against Infectious Bronchitis Provided by Recombinant Infectious Bronchitis Viruses Expressing Heterologous Spike Glycoproteins

by Sarah Keep, Samantha Sives, Phoebe Stevenson-Leggett, Paul Britton, Lonneke Vervelde and Erica Bickerton

Vaccines 2020, 8(2), 330; https://doi.org/10.3390/vaccines8020330 - 22 Jun 2020

Cited by 8 | Viewed by 4363

Abstract

Gammacoronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease of poultry. Protective immunity is associated with the major structural protein, spike (S) glycoprotein, which induces neutralising antibodies and defines the serotype. Cross-protective immunity between serotypes is limited and can be difficult [...] Read more.

Gammacoronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease of poultry. Protective immunity is associated with the major structural protein, spike (S) glycoprotein, which induces neutralising antibodies and defines the serotype. Cross-protective immunity between serotypes is limited and can be difficult to predict. In this study, the ability of two recombinant IBV vaccine candidates, BeauR-M41(S) and BeauR-4/91(S), to induce cross-protection against a third serotype, QX, was assessed. Both rIBVs are genetically based on the Beaudette genome with only the S gene derived from either M41 or 4/91, two unrelated serotypes. The use of these rIBVs allowed for the assessment of the potential of M41 and 4/91 S glycoproteins to induce cross-protective immunity against a heterologous QX challenge. The impact of the order of vaccination was also assessed. Homologous primary and secondary vaccination with BeauR-M41(S) or BeauR-4/91(S) resulted in a significant reduction of infectious QX load in the trachea at four days post-challenge, whereas heterologous primary and secondary vaccination with BeauR-M41(S) and BeauR-4/91(S) reduced viral RNA load in the conjunctiva-associated lymphoid tissue (CALT). Both homologous and heterologous vaccination regimes reduced clinical signs and birds recovered more rapidly as compared with an unvaccinated/challenge control group. Despite both rIBV BeauR-M41(S) and BeauR-4/91(S) displaying limited replication in vivo, serum titres in these vaccinated groups were higher as compared with the unvaccinated/challenge control group. This suggests that vaccination with rIBV primed the birds for a boosted humoral response to heterologous QX challenge. Collectively, vaccination with the rIBV elicited limited protection against challenge, with failure to protect against tracheal ciliostasis, clinical manifestations, and viral replication. The use of a less attenuated recombinant vector that replicates throughout the respiratory tract could be required to elicit a stronger and prolonged protective immune response. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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18 pages, 3400 KiB

Open AccessArticle

ELISA-Based Assay for Studying Major and Minor Group Rhinovirus–Receptor Interactions

by Petra Pazderova, Eva E. Waltl, Verena Niederberger-Leppin, Sabine Flicker, Rudolf Valenta and Katarzyna Niespodziana

Vaccines 2020, 8(2), 315; https://doi.org/10.3390/vaccines8020315 - 18 Jun 2020

Cited by 4 | Viewed by 3726

Abstract

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, [...] Read more.

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, and the need for preclinical models for the screening of vaccine candidates and antiviral compounds. We report the establishment and characterization of an ELISA-based assay for studying major and minor group RV–receptor interactions. This assay is based on the interaction of purified virus with plate-bound human receptor proteins, intercellular adhesion molecule 1 (ICAM-1), and low density lipoprotein receptor (LDLR). Using RV strain-specific antibodies, we demonstrate the specific binding of a panel of major and minor RV group types including RV-A and RV-B strains to ICAM-1 and LDLR, respectively. We show that the RV–receptor interaction can be blocked with receptor-specific antibodies as well as with soluble receptors and neutralizing RV-specific antibodies. The assay is more sensitive than a cell culture-based virus neutralization test. The ELISA assay will therefore be useful for the preclinical evaluation for preventive and therapeutic strategies targeting the RV–receptor interaction, such as vaccines, antibodies, and anti-viral compounds. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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21 pages, 4087 KiB

Open AccessArticle

Gut Microbiota Abrogates Anti-α-Gal IgA Response in Lungs and Protects against Experimental Aspergillus Infection in Poultry

by Lourdes Mateos-Hernández, Veronica Risco-Castillo, Edgar Torres-Maravilla, Luis G. Bermúdez-Humarán, Pilar Alberdi, Adnan Hodžić, Angelica Hernández-Jarguin, Sabine Rakotobe, Clemence Galon, Elodie Devillers, Jose de la Fuente, Jacques Guillot and Alejandro Cabezas-Cruz

Vaccines 2020, 8(2), 285; https://doi.org/10.3390/vaccines8020285 - 07 Jun 2020

Cited by 27 | Viewed by 4928

Abstract

Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-α-1,3-galactose (α-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing α-Gal regulate the immune response to this glycan [...] Read more.

Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-α-1,3-galactose (α-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing α-Gal regulate the immune response to this glycan in animals lacking endogenous α-Gal. Here, we asked whether the production of anti-α-Gal Abs in response to microbiota stimulation in birds, confers protection against infection by Aspergillus fumigatus, a major fungal pathogen that expresses α-Gal in its surface. We demonstrated that the oral administration of Escherichia coli O86:B7 strain, a bacterium with high α-Gal content, reduces the occurrence of granulomas in lungs and protects turkeys from developing acute aspergillosis. Surprisingly, the protective effect of E. coli O86:B7 was not associated with an increase in circulating anti-α-Gal IgY levels, but with a striking reduction of anti-α-Gal IgA in the lungs of infected turkeys. Subcutaneous immunization against α-Gal did not induce a significant reduction of lung anti-α-Gal IgA and failed to protect against an infectious challenge with A. fumigatus. Oral administration of E. coli O86:B7 was not associated with the upregulation of lung cytokines upon A. fumigatus infection. We concluded that the oral administration of bacteria expressing high levels of α-Gal decreases the levels of lung anti-α-Gal IgA, which are mediators of inflammation and lung damage during acute aspergillosis. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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16 pages, 4344 KiB

Open AccessArticle

Experimental PCEP-Adjuvanted Swine Influenza H1N1 Vaccine Induced Strong Immune Responses but Did Not Protect Piglets against Heterologous H3N2 Virus Challenge

by Royford Bundi Magiri, Ken John Lai, George Kiremu Mutwiri and Heather Lynne Wilson

Vaccines 2020, 8(2), 235; https://doi.org/10.3390/vaccines8020235 - 18 May 2020

Cited by 6 | Viewed by 2935

Abstract

Vaccination is the most efficient method of protection against influenza infections. However, the rapidly mutating viruses and development of new strains make it necessary to develop new influenza vaccines annually. Hence, vaccines that stimulate cross-protection against multiple influenza subtypes are highly sought. Recent [...] Read more.

Vaccination is the most efficient method of protection against influenza infections. However, the rapidly mutating viruses and development of new strains make it necessary to develop new influenza vaccines annually. Hence, vaccines that stimulate cross-protection against multiple influenza subtypes are highly sought. Recent evidence suggests that adjuvants such as PCEP that promote Th1-type T cell and Th2-type T cell immune responses and broad-spectrum immune responses may confer cross-protection against heterologous influenza strains. In this study, we evaluated whether the immunogenic and protective potential of PCEP-adjuvanted inactivated swine influenza virus H1N1 vaccine can protect pigs immunized against live H3N2 virus. Piglets were vaccinated via the intradermal route with PCEP-adjuvanted inactivated swine influenza virus (SIV) H1N1 vaccine, boosted at day 21 with the same vaccines then challenged with infectious SIV H3N2 virus at day 35 via the tracheobronchial route. The pigs showed significant anti-H1N1 SIV specific antibody titres and H1N1 SIV neutralizing antibody titres, and these serum titres remained after the challenge with the H3N2 virus. In contrast, vaccination with anti-H1N1 SIV did not trigger anti-H3N2 SIV antibody titres or neutralizing antibody titres and these titres remained low until pigs were challenged with H3N2 SIV. At necropsy (six days after challenge), we collected prescapular lymph nodes and tracheobronchial draining the vaccination sites and challenge site, respectively. ELISPOTs from lymph node cells restimulated ex vivo with inactivated SIV H1N1 showed significant production of IFN-γ in the tracheobronchial cells, but not the prescapular lymph nodes. In contrast, lymph node cells restimulated ex vivo with inactivated SIV H1N1 showed significantly higher IL-13 and IL-17A in the prescapular lymph nodes draining the vaccination sites relative to unchallenged animals. Lung lesion scores show that intradermal vaccination with H1N1 SIV plus PCEP did not prevent lesions when the animals were challenged with H3N2. These results confirm previous findings that PCEP is effective as a vaccine adjuvant in that it induces strong immune responses and protects against homologous swine influenza H1N1 virus, but the experimental H1N1 vaccine failed to cross-protect against heterologous H3N2 virus. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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26 pages, 7196 KiB

Open AccessArticle

Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models

by Wilson Nguyen, Eri Nakayama, Kexin Yan, Bing Tang, Thuy T. Le, Liang Liu, Tamara H. Cooper, John D. Hayball, Helen M. Faddy, David Warrilow, Richard J. N. Allcock, Jody Hobson-Peters, Roy A. Hall, Daniel J. Rawle, Viviana P. Lutzky, Paul Young, Nidia M. Oliveira, Gunter Hartel, Paul M. Howley, Natalie A. Prow and Andreas Suhrbier Show full author list Hide full author list

Vaccines 2020, 8(2), 209; https://doi.org/10.3390/vaccines8020209 - 05 May 2020

Cited by 19 | Viewed by 6108

Abstract

Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting [...] Read more.

Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1^-/- mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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16 pages, 2341 KiB

Open AccessArticle

Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses

by Gendeal M. Fadlallah, Fuying Ma, Zherui Zhang, Mengchan Hao, Juefu Hu, Mingxin Li, Haizhou Liu, Biling Liang, Yanfeng Yao, Rui Gong, Bo Zhang, Di Liu and Jianjun Chen

Vaccines 2020, 8(1), 143; https://doi.org/10.3390/vaccines8010143 - 23 Mar 2020

Cited by 5 | Viewed by 3529

Abstract

H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses [...] Read more.

H7 subtype avian influenza viruses have caused outbreaks in poultry, and even human infection, for decades in both Eurasia and North America. Although effective vaccines offer the best protection against avian influenza viruses, antigenically distinct Eurasian and North American lineage subtype H7 viruses require the development of cross-protective vaccine candidates. In this study, a methodology called computationally optimized broadly reactive antigen (COBRA) was used to develop four consensus H7 antigens (CH7-22, CH7-24, CH7-26, and CH7-28). In vitro experiments confirmed the binding of monoclonal antibodies to the head and stem domains of cell surface-expressed consensus HAs, indicating display of their antigenicity. Immunization with DNA vaccines encoding the four antigens was evaluated in a mouse model. Broadly reactive antibodies against H7 viruses from Eurasian and North American lineages were elicited and detected by binding, inhibition, and neutralizing analyses. Further infection with Eurasian H7N9 and North American H7N3 virus strains confirmed that CH7-22 and CH7-24 conferred the most effective protection against hetero-lethal challenge. Our data showed that the consensus H7 vaccines elicit a broadly reactive, protective response against Eurasian and North American lineage H7 viruses, which are suitable for development against other zoonotic influenza viruses. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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15 pages, 1976 KiB

Open AccessArticle

Subcutaneous Immunization of Leishmania HSP70-II Null Mutant Line Reduces the Severity of the Experimental Visceral Leishmaniasis in BALB/c Mice

by José Carlos Solana, Laura Ramírez, Emma CL Cook, Elena Hernández-García, Silvia Sacristán, M. Elena Martín, Víctor Manuel González, Rosa María Reguera, Rafael Balaña-Fouce, Manuel Fresno, José María Requena, Salvador Iborra and Manuel Soto

Vaccines 2020, 8(1), 141; https://doi.org/10.3390/vaccines8010141 - 23 Mar 2020

Cited by 14 | Viewed by 3373

Abstract

Leishmania infantum parasites cause a severe form of visceral leishmaniasis in human and viscerocutaneous leishmaniasis in dogs. Recently, we reported that immunization with an attenuated L. infantum cell line, lacking the hsp70-II gene, protects against the development of murine cutaneous leishmaniasis. In this [...] Read more.

Leishmania infantum parasites cause a severe form of visceral leishmaniasis in human and viscerocutaneous leishmaniasis in dogs. Recently, we reported that immunization with an attenuated L. infantum cell line, lacking the hsp70-II gene, protects against the development of murine cutaneous leishmaniasis. In this work, we analyzed the vaccine potential of this cell line towards the long-term protection against murine visceral leishmaniasis. This model shows an organ-dependent evolution of the disease. The infection can resolve in the liver but chronically affect spleen and bone marrow. Twelve weeks after subcutaneous administration of attenuated L. infantum, Bagg Albino (BALB/c) mice were challenged with infective L. infantum parasites expressing the luciferase-encoding gene. Combining in vivo bioimaging techniques with limiting dilution experiments, we report that, in the initial phase of the disease, vaccinated animals presented lower parasite loads than unvaccinated animals. A reduction of the severity of liver damage was also detected. Protection was associated with the induction of rapid parasite-specific IFN-γ production by CD4⁺ and CD8⁺ T cells. However, the vaccine was unable to control the chronic phase of the disease, since we did not find differences in the parasite burdens nor in the immune response at that time point. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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16 pages, 2138 KiB

Open AccessArticle

MiRNA Targeted NP Genome of Live Attenuated Influenza Vaccines Provide Cross-Protection against a Lethal Influenza Virus Infection

by Feixia Gao, Tianhan Yang, Xueying Liu, Feifei Xiong, Jian Luo, Yinglei Yi, Jiangfeng Fan, Ze Chen and Wen-Song Tan

Vaccines 2020, 8(1), 65; https://doi.org/10.3390/vaccines8010065 - 03 Feb 2020

Cited by 8 | Viewed by 2805

Abstract

The miRNA-based strategy has been used to develop live attenuated influenza vaccines. In this study, the nucleoprotein (NP) genome segment of the influenza virus was inserted by different perfect miRNA-192-5p target sites, and the virus was rescued by standard reverse genetics method, so [...] Read more.

The miRNA-based strategy has been used to develop live attenuated influenza vaccines. In this study, the nucleoprotein (NP) genome segment of the influenza virus was inserted by different perfect miRNA-192-5p target sites, and the virus was rescued by standard reverse genetics method, so as to verify the virulence and protective efficacy of live attenuated vaccine in cells and mice. The results showed there was no significant attenuation in 192t virus with one perfect miRNA-192-5p target site, and 192t-3 virus with three perfect miRNA target sites. However, 192t-6 virus with 6 perfect miRNA target sites and 192t-9 virus with 9 perfect miRNA target sites were both significantly attenuated after infection, and their virulence were similar to that of temperature-sensitive (TS) influenza A virus (IAV) which is a temperature-sensitive live attenuated influenza vaccine. Mice were immunized with different doses of 192t-6, 192t-9, and TS IAV. Four weeks after immunization, the IgG in serum and IgA in lung homogenate were increased in the 192t-6, 192t-9, and TS IAV groups, and the numbers of IFN-γ secreting splenocytes were also increased in a dose-dependent manner. Finally, 192t-6, and 192t-9 can protect the mice against the challenge of homologous PR8 H1N1 virus and heterosubtypic H3N2 influenza virus. MiRNA targeted viruses 192t-6 and 192t-9 were significantly attenuated and showed the same virulence as TS IAV and played a role in the cross-protection. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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14 pages, 1249 KiB

Open AccessArticle

Protective Immunity against Vibrio harveyi in Grouper Induced by Single Vaccination with Poly (Lactide-co-glycolide) Microparticles Releasing Pleurocidin Peptide and Recombinant Glyceraldehyde-3-phosphate Dehydrogenase

by Shang-Pin Liu, Shu-Chun Chuang and Chung-Da Yang

Vaccines 2020, 8(1), 33; https://doi.org/10.3390/vaccines8010033 - 19 Jan 2020

Cited by 2 | Viewed by 2272

Abstract

The peptide adjuvant, pleurocidin (PLE), and the Vibrio harveyi antigen, recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH) protein, were encapsulated with poly (lactide-co-glycolide) (PLG) polymers in our previous study to produce PLG-encapsulated PLE plus rGAPDH microparticles (PLG-PLE/rGAPDH MPs) that sustained stable release of both PLE [...] Read more.

The peptide adjuvant, pleurocidin (PLE), and the Vibrio harveyi antigen, recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH) protein, were encapsulated with poly (lactide-co-glycolide) (PLG) polymers in our previous study to produce PLG-encapsulated PLE plus rGAPDH microparticles (PLG-PLE/rGAPDH MPs) that sustained stable release of both PLE and rGAPDH as well as, after two-time vaccination with MPs, generated long-term protective immunity against V. harveyi in grouper. Stable controlled-release of PLE plus rGAPDH from PLG-PLE/rGAPDH MPs is an attractive feature for developing an effective single-dose vaccine. In the present study, therefore, we aim to evaluate whether single administration with PLG-PLE/rGAPDH MPs in grouper would result in protective immunity against V. harveyi. Peritoneal vaccination of grouper with one dose of PLG-PLE/rGAPDH MPs raised serum titers over a long 12-week period. Moreover, twelve weeks after vaccination, significant lymphocyte proliferation and maximum TNF-α production were found in grouper immunized with a single dose of PLG-PLE/rGAPDH MPs. More importantly, immune responses elicited by single vaccination with PLG-PLE/rGAPDH MPs protected 80% of fish against a lethal peritoneal challenge of the highly virulent V. harveyi (Vh MML-1). In conclusion, our data truly reveal the feasibility of the development of a single-dose vaccine against V. harveyi based on PLG-PLE/rGAPDH MPs. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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17 pages, 1044 KiB

Open AccessArticle

Cross-Protection Induced by a A/MAY/97 Emergency Vaccine Against Intra-Serotype Heterologous Challenge with a Foot-and-Mouth Disease Virus from the A/ASIA/G-VII Lineage

by Aldo Dekker, Beatriz Sanz-Bernardo, Nagendrakumar Balasubramanian Singanallur, Anna B. Ludi, Jacquelyn Horsington, Phaedra L. Eblé, Donald P. King and Wilna Vosloo

Vaccines 2020, 8(1), 24; https://doi.org/10.3390/vaccines8010024 - 14 Jan 2020

Cited by 7 | Viewed by 3943

Abstract

Since 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East have been caused by a new emerging viral lineage, A/ASIA/G-VII. Invitro vaccine matching data indicated that this virus poorly matched (low r₁-value) with vaccines that were being used in the [...] Read more.

Since 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East have been caused by a new emerging viral lineage, A/ASIA/G-VII. Invitro vaccine matching data indicated that this virus poorly matched (low r₁-value) with vaccines that were being used in the region as well as most other commercially available vaccines. The aim of this study was to assess the performance of two candidate vaccines against challenge with a representative field virus from the A/ASIA/G-VII lineage. The results from an initial full dose protection study provided encouraging data for the A/MAY/97 vaccine, while the A₂₂/IRQ/64 vaccine only protected 2/7 vaccinated animals. In view of these promising results, this vaccine was tested in a potency test (PD₅₀) experiment in which 5 cattle were vaccinated with a full dose, 5 cattle with a 1/3 dose and 5 cattle with a 1/9 dose of vaccine. At 21 days post vaccination these vaccinated cattle and 3 control cattle were challenged intradermolingually with a field isolate from the A/ASIA/G-VII lineage. The intra-serotype heterologous potency test resulted in an intra-serotype heterologous potency of 6.5 PD₅₀/dose. These data support previous studies showing that a high potency emergency vaccine can protect against clinical disease when challenged with a heterologous strain of the same serotype, indicating that not only the r₁-value of the vaccine, but also the homologous potency of a vaccine should be taken into account when advising vaccines to control an outbreak. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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22 pages, 1364 KiB

Open AccessReview

Progress in L2-Based Prophylactic Vaccine Development for Protection against Diverse Human Papillomavirus Genotypes and Associated Diseases

by Pola Olczak and Richard B.S. Roden

Vaccines 2020, 8(4), 568; https://doi.org/10.3390/vaccines8040568 - 01 Oct 2020

Cited by 17 | Viewed by 6314

Abstract

The human papillomaviruses (HPVs) are a family of small DNA tumor viruses including over 200 genotypes classified by phylogeny into several genera. Different genera of HPVs cause ano-genital and oropharyngeal cancers, skin cancers, as well as benign diseases including skin and genital warts. [...] Read more.

The human papillomaviruses (HPVs) are a family of small DNA tumor viruses including over 200 genotypes classified by phylogeny into several genera. Different genera of HPVs cause ano-genital and oropharyngeal cancers, skin cancers, as well as benign diseases including skin and genital warts. Licensed vaccines composed of L1 virus-like particles (VLPs) confer protection generally restricted to the ≤9 HPV types targeted. Here, we examine approaches aimed at broadening the protection against diverse HPV types by targeting conserved epitopes of the minor capsid protein, L2. Compared to L1 VLP, L2 is less immunogenic. However, with appropriate presentation to the immune system, L2 can elicit durable, broadly cross-neutralizing antibody responses and protection against skin and genital challenge with diverse HPV types. Such approaches to enhance the strength and breadth of the humoral response include the display of L2 peptides on VLPs or viral capsids, bacteria, thioredoxin and other platforms for multimerization. Neither L2 nor L1 vaccinations elicit a therapeutic response. However, fusion of L2 with early viral antigens has the potential to elicit both prophylactic and therapeutic immunity. This review of cross-protective HPV vaccines based on L2 is timely as several candidates have recently entered early-phase clinical trials. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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21 pages, 1559 KiB

Open AccessReview

Cross-Protection of Hepatitis B Vaccination among Different Genotypes

by Takako Inoue and Yasuhito Tanaka

Vaccines 2020, 8(3), 456; https://doi.org/10.3390/vaccines8030456 - 16 Aug 2020

Cited by 24 | Viewed by 7346

Abstract

Hepatitis B (HB) vaccination is the most effective method for preventing HB virus (HBV) infection. Universal HB vaccination containing recombinant HB surface antigens (HBsAg) is recommended. Our data revealed that human monoclonal HB surface antibody (anti-HBs) from individuals inoculated with genotype C-based HB [...] Read more.

Hepatitis B (HB) vaccination is the most effective method for preventing HB virus (HBV) infection. Universal HB vaccination containing recombinant HB surface antigens (HBsAg) is recommended. Our data revealed that human monoclonal HB surface antibody (anti-HBs) from individuals inoculated with genotype C-based HB vaccine induced cross-protection against HBV genotype A infection. An in vitro infection model demonstrated anti-HBs-positive sera from individuals inoculated with genotype A- or C-based HB vaccine harbored polyclonal anti-HBs that could bind to non-vaccinated genotype HBV. However, because there were low titers of anti-HBs specific for HBsAg of non-vaccinated genotype, high anti-HBs titers would be required to prevent non-vaccinated genotype HBV infection. Clinically, the 2015 Centers for Disease Control and Prevention guidelines state that periodic monitoring of anti-HBs levels after routine HB vaccination is not needed and that booster doses of HB vaccine are not recommended. However, the American Red Cross suggests that HB-vaccine-induced immune memory might be limited; although HB vaccination can prevent clinical liver injury (hepatitis), subclinical HBV infections of non-vaccinated genotypes resulting in detectable HB core antibody could not be completely prevented. Therefore, monitoring anti-HBs levels after routine vaccination might be necessary for certain subjects in high-risk groups. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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23 pages, 388 KiB

Open AccessReview

Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine

by Christopher E. Lopez and Kevin L. Legge

Vaccines 2020, 8(3), 434; https://doi.org/10.3390/vaccines8030434 - 03 Aug 2020

Cited by 23 | Viewed by 5752

Abstract

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, [...] Read more.

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

15 pages, 1319 KiB

Open AccessReview

Broadly Neutralizing Antibodies for Influenza: Passive Immunotherapy and Intranasal Vaccination

by Mrityunjoy Biswas, Tatsuya Yamazaki, Joe Chiba and Sachiko Akashi-Takamura

Vaccines 2020, 8(3), 424; https://doi.org/10.3390/vaccines8030424 - 29 Jul 2020

Cited by 12 | Viewed by 4460

Abstract

Influenza viruses cause annual epidemics and occasional pandemics. The high diversity of viral envelope proteins permits viruses to escape host immunity. Therefore, the development of a universal vaccine and broadly neutralizing antibodies (bnAbs) is essential for controlling various mutant viruses. Here, we review [...] Read more.

Influenza viruses cause annual epidemics and occasional pandemics. The high diversity of viral envelope proteins permits viruses to escape host immunity. Therefore, the development of a universal vaccine and broadly neutralizing antibodies (bnAbs) is essential for controlling various mutant viruses. Here, we review some potentially valuable bnAbs for influenza; one is a novel passive immunotherapy using a variable domain of heavy chain-only antibody (V_HH), and the other is polymeric immunoglobulin A (pIgA) induced by intranasal vaccination. Recently, it was reported that a tetravalent multidomain antibody (MDAb) was developed by genetic fusion of four V_HHs, which are bnAbs against the influenza A or B viruses. The transfer of a gene encoding the MDAb–Fc fusion protein provided cross-protection against both influenza A and B viruses in vivo. An intranasal universal influenza vaccine, which can induce neutralizing pIgAs in the upper respiratory tract, is currently undergoing clinical studies. A recent study has revealed that tetrameric IgAs formed in nasal mucosa are more broadly protective against influenza than the monomeric and dimeric forms. These broadly neutralizing antibodies have high potential to control the currently circulating influenza virus. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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16 pages, 683 KiB

Open AccessReview

Pre-Erythrocytic Vaccines against Malaria

by Camila Marques-da-Silva, Kristen Peissig and Samarchith P. Kurup

Vaccines 2020, 8(3), 400; https://doi.org/10.3390/vaccines8030400 - 21 Jul 2020

Cited by 19 | Viewed by 5517

Abstract

Malaria, caused by the protozoan Plasmodium, is a devastating disease with over 200 million new cases reported globally every year. Although immunization is arguably the best strategy to eliminate malaria, despite decades of research in this area we do not have an effective, [...] Read more.

Malaria, caused by the protozoan Plasmodium, is a devastating disease with over 200 million new cases reported globally every year. Although immunization is arguably the best strategy to eliminate malaria, despite decades of research in this area we do not have an effective, clinically approved antimalarial vaccine. The current impetus in the field is to develop vaccines directed at the pre-erythrocytic developmental stages of Plasmodium, utilizing novel vaccination platforms. We here review the most promising pre-erythrocytic stage antimalarial vaccine candidates. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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9 pages, 711 KiB

Open AccessReview

Japan’s Ongoing Crisis on HPV Vaccination

by Masayuki Sekine, Risa Kudo, Manako Yamaguchi, Sharon J. B. Hanley, Megumi Hara, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Sayaka Ikeda, Asami Yagi and Takayuki Enomoto

Vaccines 2020, 8(3), 362; https://doi.org/10.3390/vaccines8030362 - 06 Jul 2020

Cited by 18 | Viewed by 5117

Abstract

The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported a high vaccine effectiveness in the group of [...] Read more.

The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported a high vaccine effectiveness in the group of women vaccinated before their first intercourse (93.9%). The prevalence of cross-protected types of HPV 31/45/52 was also lower in the vaccinated group, and the vaccine effectiveness was 67.7%. Furthermore, prevalence of HPV16, 31 and 52 infection rates in the vaccinated group were obviously lower than that in the unvaccinated group, and no one had HPV18 or 45 infection in the vaccinated group. The addition of a cross-protective effect toward HPV types 31/45/52 to HPV types 16/18, which is the direct target of the bivalent HPV vaccine, may possibly prevent around 82% of invasive cervical cancer cases in Japan. With regard to the preventive effect of histological abnormalities, we also reported significant reduction in incidence of cervical intraepithelial neoplasia (CIN)3 or worse. Thus, the efficacy of the vaccine has been demonstrated for precancerous disease, and the diverse symptoms after HPV vaccination are likely functional somatic. For the future of Japanese girls, there is a need to resume the proactive recommendation of HPV vaccination and for immediate action to be taken by the Japanese government. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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12 pages, 2012 KiB

Open AccessReview

Prospects and Challenges in the Development of Universal Influenza Vaccines

by Anders Madsen and Rebecca Jane Cox

Vaccines 2020, 8(3), 361; https://doi.org/10.3390/vaccines8030361 - 06 Jul 2020

Cited by 18 | Viewed by 5216

Abstract

Current influenza vaccines offer suboptimal protection and depend on annual reformulation and yearly administration. Vaccine technology has rapidly advanced during the last decade, facilitating development of next-generation influenza vaccines that can target a broader range of influenza viruses. The development and licensure of [...] Read more.

Current influenza vaccines offer suboptimal protection and depend on annual reformulation and yearly administration. Vaccine technology has rapidly advanced during the last decade, facilitating development of next-generation influenza vaccines that can target a broader range of influenza viruses. The development and licensure of a universal influenza vaccine could provide a game changing option for the control of influenza by protecting against all influenza A and B viruses. Here we review important findings and considerations regarding the development of universal influenza vaccines and what we can learn from this moving forward with a SARS-CoV-2 vaccine design. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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