Vaccine protection against SIVmac239 acquisition

The biological characteristics of HIV pose serious difficulties for the success of a preventive vaccine. Molecularly cloned SIVmac239 is difficult for antibodies to neutralize, and a variety of vaccine approaches have had great difficulty achieving protective immunity against it in rhesus monkey models. Here we report significant protection against i.v. acquisition of SIVmac239 using a long-lasting approach to vaccination. The vaccine regimen includes a replication-competent herpesvirus engineered to contain a near-full-length SIV genome that expresses all nine SIV gene products, assembles noninfectious SIV virion particles, and is capable of eliciting long-lasting effector-memory cellular immune responses to all nine SIV gene products. Vaccinated monkeys were significantly protected against acquisition of SIVmac239 following repeated marginal dose i.v. challenges over a 4-month period. Further work is needed to define the critical components necessary for eliciting this protective immunity, evaluate the breadth of the protection against a variety of strains, and explore how this approach may be extended to human use.

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SARS-COV-2 Recombinant Receptor-Binding-Domain (RBD) Induces Neutralising Antibodies Against Variant Strains of SARS-CoV-2 and SARS-CoV-1

10.1101/2021.05.10.443438 ◽

2021 ◽

Author(s):

John Lok Man Law ◽

Michael Logan ◽

Michael Joyce ◽

Abdolamir Landi ◽

Darren Hockman ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Antigen ◽

Neutralising Antibodies ◽

Cellular Immune Responses ◽

Recombinant Receptor ◽

Virion Envelope ◽

Human Use ◽

Cellular Immune

SARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them are targeting the spike protein (or virion) in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralization in vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested the utility of SARS-CoV-2 spike RBD as a vaccine antigen and explore the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results indicate RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralisation of variants B1.1.7 and B.1.351 and to a lesser extent, SARS-CoV- 1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.

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Envelope Determinants of Equine Infectious Anemia Virus Vaccine Protection and the Effects of Sequence Variation on Immune Recognition

Journal of Virology ◽

10.1128/jvi.02028-07 ◽

2008 ◽

Vol 82 (8) ◽

pp. 4052-4063 ◽

Cited By ~ 21

Author(s):

Tara L. Tagmyer ◽

Jodi K. Craigo ◽

Sheila J. Cook ◽

Deborah L. Even ◽

Charles J. Issel ◽

...

Keyword(s):

Immune Responses ◽

Protective Immunity ◽

Equine Infectious Anemia Virus ◽

Immune Recognition ◽

Vaccine Protection ◽

Challenge Strain ◽

Cellular Immune Responses ◽

Equine Infectious Anemia ◽

Anemia Virus ◽

Cellular Immune

ABSTRACT A highly effective attenuated equine infectious anemia virus (EIAV) vaccine (EIAVD9) capable of protecting 100% of horses from disease induced by a homologous Env challenge strain (EIAVPV) was recently tested in ponies to determine the level of protection against divergent Env challenge strains (J. K. Craigo, B. S. Zhang, S. Barnes, T. L. Tagmyer, S. J. Cook, C. J. Issel, and R. C. Montelaro, Proc. Natl. Acad. Sci. USA 104:15105-15110, 2007). An inverse correlation between challenge strain Env variation and vaccine protection from disease was observed. Given the striking differences in protective immunity, we hypothesized that analysis of the humoral and cellular immune responses to the Env protein could reveal potential determinants of vaccine protection. Neutralization activity against the homologous Env or challenge strain-specific Env in immune sera from the vaccinated ponies did not correlate with protection from disease. Cellular analysis with Env peptide pools did not reveal an association with vaccine protection from disease. However, when individual vaccine-specific Env peptides were utilized, eight cytotoxic-T-lymphocyte (CTL) peptides were found to associate closely with vaccine protection. One of these peptides also yielded the only lymphoproliferative response associated with protective immunity. The identified peptides spanned both variable and conserved regions of gp90. Amino acid divergence within the principal neutralization domain and the identified peptides profoundly affected immune recognition, as illustrated by the inability to detect cross-reactive neutralizing antibodies and the observation that certain peptide-specific CTL responses were altered. In addition to identifying potential Env determinants of EIAV vaccine efficacy and demonstrating the profound effects of defined Env variation on immune recognition, these data also illustrate the sensitivity offered by individual peptides compared to peptide pools in measuring cellular immune responses in lentiviral vaccine trials.

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Protective Efficacy of an Inactive Vaccine Based on the LY02 Isolate against AcuteHaemophilus parasuisInfection in Piglets

BioMed Research International ◽

10.1155/2015/649878 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Xiao-Hua Li ◽

Guo-Zhen Zhao ◽

Long-Xin Qiu ◽

Ai-Ling Dai ◽

Wang-Wei Wu ◽

...

Keyword(s):

Immune Responses ◽

Protective Immunity ◽

Protective Efficacy ◽

Haemophilus Parasuis ◽

Fujian Province ◽

Cellular Immune Responses ◽

Glässer’S Disease ◽

Potential Vaccine ◽

Cellular Immune ◽

Glasser's Disease

Haemophilus parasuiscan cause Glässer’s disease characterized by fibrinous polyserositis, polyarthritis, and meningitis. The current prevention of Glässer’s disease is mainly based on the inactive vaccines; however, the protective efficacy usually fails in heterogeneous or homologous challenges. Here, the predominant lineage ofH. parasuis(LY02 strain) in Fujian province, China, characterized as serovar 5, was used to evaluate the protective immunity against acuteH. parasuisinfection in piglets after inactivation. Following challenging withH. parasuis,only mild lesions in the pigs immunized with the killed vaccine were observed, whereas the typical symptoms of Glässer’s disease presented in the nonimmunized piglets. A strong IgG immune response was induced by the inactive vaccine. CD4+and CD8+T lymphocyte levels were increased, indicating the potent cellular immune responses were elicited. The significantly high levels of IL-2, IL-4, TGF-β, and IFN-γin sera from pigs immunized with this killed vaccine suggested that the mixed Th1 and Th2 immune responses were induced, associated with the high protection againstH. parasuisinfection compared to the nonimmunized animals. This study indicated that the inactivated LY02 strain ofH. parasuiscould serve as a potential vaccine candidate to prevent the prevalence ofH. parasuisin Fujian province, China.

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Intrarectal Immunization with Rotavirus 2/6 Virus-Like Particles Induces an Antirotavirus Immune Response Localized in the Intestinal Mucosa and Protects against Rotavirus Infection in Mice

Journal of Virology ◽

10.1128/jvi.80.8.3823-3832.2006 ◽

2006 ◽

Vol 80 (8) ◽

pp. 3823-3832 ◽

Cited By ~ 41

Author(s):

Davide Agnello ◽

Christine A. Hervé ◽

Amandine Lavaux ◽

Magali Darniot ◽

Patrice Guillon ◽

...

Keyword(s):

Immune Response ◽

Intestinal Mucosa ◽

Protective Immunity ◽

Ex Vivo ◽

Cellular Immune Responses ◽

Adult Mice ◽

Specific Immunoglobulin ◽

Severe Gastroenteritis ◽

Iga Production ◽

Cellular Immune

ABSTRACT Rotavirus (RV) is the main etiological agent of severe gastroenteritis in infants, and vaccination seems the most effective way to control the disease. Recombinant rotavirus-like particles composed of the viral protein 6 (VP6) and VP2 (2/6-VLPs) have been reported to induce protective immunity in mice when administered by the intranasal (i.n.) route. In this study, we show that administration of 2/6-VLPs by the intrarectal (i.r.) route together with either cholera toxin (CT) or a CpG-containing oligodeoxynucleotide as the adjuvant protects adult mice against RV infection. Moreover, when CT is used, RV shedding in animals immunized by the i.r. route is even reduced in comparison with that in animals immunized by the i.n. route. Humoral and cellular immune responses induced by these immunization protocols were analyzed. We found that although i.r. immunization with 2/6-VLPs induces lower RV-specific immunoglobulin G (IgG) and IgA levels in serum, intestinal anti-RV IgA production is higher in mice immunized by the i.r. route. Cellular immune response has been evaluated by measuring cytokine production by spleen and Peyer's patch cells (PPs) after ex vivo restimulation with RV. Mice immunized by the i.n. and i.r. routes display higher gamma interferon production in spleen and PPs, respectively. In conclusion, we demonstrate that i.r. immunization with 2/6-VLPs protects against RV infection in mice and is more efficient than i.n. immunization in inducing an anti-RV immune response in intestinal mucosa.

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Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

10.21203/rs.3.rs-40198/v1 ◽

2020 ◽

Author(s):

Flavia Chiuppesi ◽

Marcela d’Alincourt Salazar ◽

Heidi Contreras ◽

Vu Nguyen ◽

Joy Martinez ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Candidate ◽

Vaccine Platform ◽

Synthetic Dna ◽

Cellular Immune Responses ◽

Global Pandemic ◽

Immunodominant Antigens ◽

Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

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Distribution difference of colostrum-derived B and T cells subsets in gilts and sows

PLoS ONE ◽

10.1371/journal.pone.0249366 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0249366

Author(s):

Ricardo Forner ◽

Gabrielly Bombassaro ◽

Franciana Volpato Bellaver ◽

Shaiana Maciag ◽

Francisco Noé Fonseca ◽

...

Keyword(s):

T Cells ◽

Neutralizing Antibodies ◽

Lymphocyte Subsets ◽

Central Memory ◽

Effector Memory ◽

T Lymphocyte Subsets ◽

Cellular Immune Responses ◽

Leukocyte Counts ◽

Leukocyte Populations ◽

Cellular Immune

Piglets are highly vulnerable to infections, but colostrum provides them with some protection. The function of colostrum components is unknown, as is if the amount and subsets of leukocytes in colostrum differ between gilts and sows. This study serially characterized leukocyte populations in colostrum for differential leukocyte counts. Differences in humoral and cellular composition of colostrum between 40 gilts and 40 sows (parities orders 3–4) from a commercial herd were examined. Flow cytometry is a useful tool to identify and quantify leukocyte subsets in sow colostrum. Overall, there were no (p ≥ 0.05) parity differences in total macrophages, granulocytes, and T and B cells. However, the sows’ colostrum presented significantly higher (p ≤ 0.05) T lymphocyte subsets than gilts, such as central memory CD4+T cells, effector memory CD4+T cells, and central memory CD8+T cells. Among B-lymphocytes, percentages of SWC7+CD5+ cells were significantly higher in sow colostrum than in that of gilts. As expected, IgG concentrations were significantly higher in sows than in gilts. Colostrum from sows had significantly greater mitogenic activity than colostrum from gilts and this fact can be associated with the potential to accelerate the maturation of a newborn’s gastrointestinal tract. Our findings suggest that parity order may be one among other factors influencing the cell population and, consequently, the immune adaptive response in piglets that induces neutralizing antibodies and cellular immune responses to antigens.

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Simian T Lymphotropic Virus 1 Infection of Papio anubis: tax Sequence Heterogeneity and T Cell Recognition

Journal of Virology ◽

10.1128/jvi.00950-17 ◽

2017 ◽

Vol 91 (20) ◽

Cited By ~ 1

Author(s):

James M. Termini ◽

Diogo M. Magnani ◽

Helen S. Maxwell ◽

William Lauer ◽

Iris Castro ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

T Lymphotropic Virus ◽

T Cell Recognition ◽

Cellular Immune Responses ◽

Htlv Infection ◽

Preventive Vaccine ◽

T Cell Lines ◽

Cellular Immune ◽

Major Target

ABSTRACT Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8+ T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. IMPORTANCE It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A preventive vaccine would significantly impact the global burden associated with HTLV infections. Here we provide fundamental information on the simian T lymphotropic virus (STLV) naturally transmitted in a colony of captive baboons. The limited viral sequence heterogeneity in individual baboons, the identity of the viral gene product that is the major target of cellular immune responses, the persistence of viral amino acid sequences that are the major targets of cellular immune responses, and the emergence in vivo of truncated variants in the major target of cellular immune responses all parallel what are seen with HTLV infection of humans. These results justify the use of STLV-infected baboons as a model system for vaccine development efforts.

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Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

Nature Communications ◽

10.1038/s41467-020-19819-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Flavia Chiuppesi ◽

Marcela d’Alincourt Salazar ◽

Heidi Contreras ◽

Vu H. Nguyen ◽

Joy Martinez ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Candidate ◽

Vaccine Platform ◽

Synthetic Dna ◽

Cellular Immune Responses ◽

Global Pandemic ◽

Immunodominant Antigens ◽

Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

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Resolving the Paradox of Colon Cancer Through the Integration of Genetics, Immunology, and the Microbiota

Frontiers in Immunology ◽

10.3389/fimmu.2020.600886 ◽

2020 ◽

Vol 11 ◽

Author(s):

Marine Fidelle ◽

Satoru Yonekura ◽

Marion Picard ◽

Alexandria Cogdill ◽

Antoine Hollebecque ◽

...

Keyword(s):

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Effector Memory ◽

Mesenteric Lymph Nodes ◽

Normal Epithelium ◽

Cell Responses ◽

Cellular Immune Responses ◽

Mesenteric Lymph ◽

Specific Memory ◽

Cellular Immune

While colorectal cancers (CRC) are paradigmatic tumors invaded by effector memory lymphocytes, the mechanisms accounting for the relative resistance of MSI negative CRC to immunogenic cell death mediated by oxaliplatin and immune checkpoint inhibitors has remained an open conundrum. Here, we propose the viewpoint where its microenvironmental contexture could be explained -at least in part- by macroenvironmental cues constituted by the complex interplay between the epithelial barrier, its microbial ecosystem, and the local immune system. Taken together this dynamic ménage-à-trois offers novel coordinated actors of the humoral and cellular immune responses actionable to restore sensitivity to immune checkpoint inhibition. Solving this paradox involves breaking tolerance to crypt stem cells by inducing the immunogenic apoptosis of ileal cells in the context of an ileal microbiome shifted towards immunogenic bacteria using cytotoxicants. This manoeuver results in the elicitation of a productive Tfh and B cell dialogue in mesenteric lymph nodes culminating in tumor-specific memory CD8+ T cell responses sparing the normal epithelium.

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Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

10.1101/2020.07.01.183236 ◽

2020 ◽

Cited By ~ 1

Author(s):

Flavia Chiuppesi ◽

Marcela d’Alincourt Salazar ◽

Heidi Contreras ◽

Vu H Nguyen ◽

Joy Martinez ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Candidate ◽

Vaccine Platform ◽

Synthetic Dna ◽

Cellular Immune Responses ◽

Global Pandemic ◽

Immunodominant Antigens ◽

Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

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