scholarly journals Biological sex affects vaccine efficacy and protection against influenza in mice

2018 ◽  
Vol 115 (49) ◽  
pp. 12477-12482 ◽  
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.

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

2017 ◽  
Vol 214 (9) ◽  
pp. 2563-2572 ◽  
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.

scholarly journals Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

2015 ◽  
Vol 23 (2) ◽  
pp. 84-94 ◽  
Author(s):  
David R. Martinez ◽  
Sallie R. Permar ◽  
Genevieve G. Fouda
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
Vaccine Efficacy ◽  
Neutralizing Antibody ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Hiv Vaccines ◽  
Vaccine Candidates ◽  
Protective Antibodies ◽  
Pediatric Populations

ABSTRACTExtensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

scholarly journals Improved Elicitation of Neutralizing Antibodies against Primary Human Immunodeficiency Viruses by Soluble Stabilized Envelope Glycoprotein Trimers

2001 ◽  
Vol 75 (3) ◽  
pp. 1165-1171 ◽  
Author(s):  
Xinzhen Yang ◽  
Richard Wyatt ◽  
Joseph Sodroski
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Viruses ◽  
Functional Envelope ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus (HIV-1) envelope glycoprotein subunits, such as the gp120 exterior glycoprotein, typically elicit antibodies that neutralize T-cell-line-adapted (TCLA), but not primary, clinical isolates of HIV-1. Here we compare the immunogenicity of gp120 and soluble stabilized trimers, which were designed to resemble the functional envelope glycoprotein oligomers of primary and TCLA HIV-1 strains. For both primary and TCLA virus proteins, soluble stabilized trimers generated neutralizing antibody responses more efficiently than gp120 did. Trimers derived from a primary isolate elicited antibodies that neutralized primary and TCLA HIV-1 strains. By contrast, trimers derived from a TCLA isolate generated antibodies that neutralized only the homologous TCLA virus. Thus, soluble stabilized envelope glycoprotein trimers derived from primary HIV-1 isolates represent defined immunogens capable of eliciting neutralizing antibodies that are active against clinically relevant HIV-1 strains.

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

Med ◽  
2021 ◽  
Author(s):  
Shirin Kalimuddin ◽  
Christine YL. Tham ◽  
Martin Qui ◽  
Ruklanthi de Alwis ◽  
Jean XY. Sim ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccine Efficacy ◽  
Antibody Responses ◽  
Binding Antibody ◽  
Rna Vaccine

scholarly journals Comparison of Human H3N2 Antibody Responses Elicited by Egg-Based, Cell-Based, and Recombinant Protein–Based Influenza Vaccines During the 2017–2018 Season

2019 ◽  
Vol 71 (6) ◽  
pp. 1447-1453 ◽  
Author(s):  
Sigrid Gouma ◽  
Seth J Zost ◽  
Kaela Parkhouse ◽  
Angela Branche ◽  
David J Topham ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Influenza Vaccines ◽  
Vaccine Antigen ◽  
H3n2 Virus ◽  
High Dose ◽  
Wild Type ◽  
H1n1 Vaccine ◽  
Antibody Titers

Abstract Background The H3N2 component of egg-based 2017–2018 influenza vaccines possessed an adaptive substitution that alters antigenicity. Several influenza vaccines include antigens that are produced through alternative systems, but a systematic comparison of different vaccines used during the 2017–2018 season has not been completed. Methods We compared antibody responses in humans vaccinated with Fluzone (egg-based, n = 23), Fluzone High-Dose (egg-based, n = 16), Flublok (recombinant protein–based, n = 23), or Flucelvax (cell-based, n = 23) during the 2017–2018 season. We completed neutralization assays using an egg-adapted H3N2 virus, a cell-based H3N2 virus, wild-type 3c2.A and 3c2.A2 H3N2 viruses, and the H1N1 vaccine strain. We also performed enzyme-linked immunosorbent assays using a recombinant wild-type 3c2.A hemagglutinin. Antibody responses were compared in adjusted analysis. Results Postvaccination neutralizing antibody titers to 3c2.A and 3c2.A2 were higher in Flublok recipients compared with Flucelvax or Fluzone recipients (P < .01). Postvaccination titers to 3c2.A and 3c2.A2 were similar in Flublok and Fluzone High-Dose recipients, though seroconversion rates trended higher in Flublok recipients. Postvaccination titers in Flucelvax recipients were low to all H3N2 viruses tested, including the cell-based H3N2 strain. Postvaccination neutralizing antibody titers to H1N1 were similar among the different vaccine groups. Conclusions These data suggest that influenza vaccine antigen match and dose are both important for eliciting optimal H3N2 antibody responses in humans. Future studies should be designed to determine if our findings directly impact vaccine effectiveness. Clinical Trials Registration NCT03068949.

Strong Cytotoxic T Cell and Weak Neutralizing Antibody Responses in a Subset of Persons with Stable Nonprogressing HIV Type 1 Infection

1996 ◽  
Vol 12 (7) ◽  
pp. 585-592 ◽  
Author(s):  
THOMAS HARRER ◽  
ELLEN HARRER ◽  
SPYROS A. KALAMS ◽  
TAREK ELBEIK ◽  
SILVIJA I. STAPRANS ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Cytotoxic T Cell ◽  
Hiv Type 1

scholarly journals Durable Humoral and Cellular Immune Responses Following Ad26.COV2.S Vaccination for COVID-19

2021 ◽  
Author(s):  
Dan H. Barouch ◽  
Kathryn Stephenson ◽  
Jerald Sadoff ◽  
Jingyou Yu ◽  
Aiquan Chang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Single Shot ◽  
Efficacy Data ◽  
Vaccine Regimen ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine for COVID-19 have recently been reported. We describe here the 8-month durability of humoral and cellular immune responses in 20 individuals who received one or two doses of 5x10^10 vp or 10^11 vp Ad26.COV2.S and in 5 participants who received placebo. We evaluated antibody and T cell responses on day 239, which was 8 months after the single-shot vaccine regimen (N=10) or 6 months after the two-shot vaccine regimen (N=10), although the present study was not powered to compare these regimens. We also report neutralizing antibody responses against the parental SARS-CoV-2 WA1/2020 strain as well as against the SARS-CoV-2 variants D614G, B.1.1.7 (alpha), B.1.617.1 (kappa), B.1.617.2 (delta), P.1 (gamma), B.1.429 (epsilon), and B.1.351 (beta).

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

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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