Early T cell and binding antibody responses are associated with Covid-19 RNA vaccine efficacy onset

Abstract A significant correlation has been shown between the binding antibody responses against original SARS-CoV-2-S-protein all performed in one laboratory and vaccine efficacy of four approved COVID-19 vaccines. We therefore assessed the immune response against original SARS-CoV-2 elicited by the adjuvanted S-Trimer vaccine, SCB-2019 + CpG/alum, in the same assay and laboratory. When compared with four approved vaccines immune responses to SCB-2019 predicted 81% − 94% efficacy against the original strain and 75–94% against the Alpha variant (B.1.1.7). Immunogenicity comparisons to original strain and variants of concern (VOC) should be considered as a basis for authorization of vaccines because efficacy studies now have predominantly VOC cases.

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Biological sex affects vaccine efficacy and protection against influenza in mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1805268115 ◽

2018 ◽

Vol 115 (49) ◽

pp. 12477-12482 ◽

Cited By ~ 39

Author(s):

Ashley L. Fink ◽

Kyrra Engle ◽

Rebecca L. Ursin ◽

Wan-Yee Tang ◽

Sabra L. Klein

Keyword(s):

T Cell ◽

Vaccine Efficacy ◽

Influenza Infection ◽

Neutralizing Antibody ◽

Antibody Responses ◽

H1n1 Vaccine ◽

Biological Sex ◽

Variant Virus ◽

Males And Females ◽

Antibody Class

Biological sex affects adaptive immune responses, which could impact influenza infection and vaccine efficacy. Infection of mice with 2009 H1N1 induced antibody responses, CD4+T cell and CD8+T cell memory responses that were greater in females than males; both sexes, however, were equally protected against secondary challenge with an H1N1 drift variant virus. To test whether greater antibody in females is sufficient for protection against influenza, males and females were immunized with an inactivated H1N1 vaccine that induced predominantly antibody-mediated immunity. Following vaccination, females had greater antibody responses and protection against challenge with an H1N1 drift variant virus than males. Antibody derived from vaccinated females was better at protecting both naïve males and females than antibody from males, and this protection was associated with increased antibody specificity and avidity to the H1N1 virus. The expression ofTlr7was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in theTlr7promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion ofTlr7reduced sex differences in vaccine-induced antibody responses and protection following challenge and had a greater impact on responses in females than males. Taken together, these data illustrate that greater TLR7 activation and antibody production in females improves the efficacy of vaccination against influenza.

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2904. Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.182 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S84-S84

Author(s):

Brett W Jagger ◽

Kimberly A Dowd ◽

Rita Chen ◽

Pritesh Desai ◽

Sunny Himansu ◽

...

Keyword(s):

T Cell ◽

Nucleic Acid ◽

Plasmid Dna ◽

Zika Virus ◽

Vaccine Efficacy ◽

Protective Efficacy ◽

Cd8 T Cell ◽

Antibody Responses ◽

Cell Vaccine ◽

Nucleic Acid Vaccines

Abstract Background Zika virus (ZIKV) caused an epidemic of microcephaly and congenital malformations in 2015–2016, prompting the development of ZIKV vaccines. Plasmid DNA and modified mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccines were among the first to reach human clinical trials, where their evaluation is ongoing. Few studies have evaluated vaccine efficacy in the setting of infection during pregnancy, and there is an open question around antibody-dependent enhancement (ADE) of flaviviral disease due to cross-reactive fusion loop epitope (FLE) antibodies. Methods Female C57BL/6J mice and human STAT2 knock-in (hSTAT2-KI) mice were immunized with plasmid DNA (VRC5283) or mRNA-LNP (Moderna Inc.) vaccines encoding the ZIKV prM-E genes. Antibody responses were assayed, and immunized mice were mated and WT mice were transiently immunocompromised by administration of interferon blocking antibody, followed by ZIKV challenge. 1 week post-infection, ZIKV burden was measured via qRT-PCR. ZIKV-specific memory B cell (MBC), long-lived plasma cell (LLPC), and CD8+ T cell vaccine responses were also assayed. Results VRC5283 and mRNA-LNP vaccines were highly immunogenic, eliciting serum neutralizing EC50 responses >1:10,000, and markedly reduced placental ZIKV burden and fetal transmission. An improved mRNA-LNP construct with higher immunogenicity correlated with reduced placental viral burden. Significantly, an FLE-mutant mRNA-LNP vaccine yielded comparable EC50 responses without compromising vaccine efficacy; sera from these mice did not enhance dengue virus infection in vitro. Both VRC5283 and mRNA-LNP vaccines elicited MBC, LLPC, and CD8+ T cell responses, although MBC and LLPC responses were greater after mRNA-LNP immunization. Surprisingly, low-level ZIKV infection of the placenta and a minority of fetal heads were observed despite robust neutralizing antibody responses, which was not seen in the immunocompetent hSTAT2-KI model. Conclusion Nucleic acid vaccines were highly immunogenic and protective against vertical ZIKV transmission during pregnancy in mice. These data support and inform the ongoing clinical development of these vaccines in humans. Disclosures All Authors: No reported Disclosures.

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RV144 HIV-1 vaccination impacts post-infection antibody responses

PLoS Pathogens ◽

10.1371/journal.ppat.1009101 ◽

2020 ◽

Vol 16 (12) ◽

pp. e1009101

Author(s):

Thembi Mdluli ◽

Ningbo Jian ◽

Bonnie Slike ◽

Dominic Paquin-Proulx ◽

Gina Donofrio ◽

...

Keyword(s):

B Cell ◽

Vaccine Efficacy ◽

Post Infection ◽

Neutralizing Antibodies ◽

Antibody Responses ◽

Functional Responses ◽

Binding Antibody ◽

Hiv 1 ◽

Rv144 Vaccine ◽

Placebo Recipients

The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.

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An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates

Science Translational Medicine ◽

10.1126/scitranslmed.abc9396 ◽

2020 ◽

Vol 12 (555) ◽

pp. eabc9396 ◽

Cited By ~ 20

Author(s):

Jesse H. Erasmus ◽

Amit P. Khandhar ◽

Megan A. O’Connor ◽

Alexandra C. Walls ◽

Emily A. Hemann ◽

...

Keyword(s):

T Cell ◽

Intramuscular Injection ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

T Cell Responses ◽

Inorganic Nanoparticles ◽

Antibody Responses ◽

S Protein ◽

Cell Responses ◽

Rna Vaccine

The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale up. Here, we developed an Alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti–SARS-CoV-2 S protein IgG antibody isotypes indicative of a type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.

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A helping hand from neutrophils in T cell–independent antibody responses?

Nature Immunology ◽

10.1038/ni.2214 ◽

2012 ◽

Vol 13 (2) ◽

pp. 111-113 ◽

Cited By ~ 1

Author(s):

Stuart G Tangye ◽

Robert Brink

Keyword(s):

T Cell ◽

Antibody Responses

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Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

Journal of Experimental Medicine ◽

10.1084/jem.20170161 ◽

2017 ◽

Vol 214 (9) ◽

pp. 2563-2572 ◽

Cited By ~ 9

Author(s):

Spencer W. Stonier ◽

Andrew S. Herbert ◽

Ana I. Kuehne ◽

Ariel Sobarzo ◽

Polina Habibulin ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Ebola Virus ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cd8 T Cell ◽

Marburg Virus ◽

Antibody Responses ◽

Cd4 T Cell ◽

Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

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