scholarly journals Soluble Proteins Induce Strong CD8+T Cell and Antibody Responses through Electrostatic Association with Simple Cationic or Anionic Lipopeptides That Target TLR2

2011 ◽  
Vol 187 (4) ◽  
pp. 1692-1701 ◽  
Author(s):  
Brendon Y. Chua ◽  
David Pejoski ◽  
Stephen J. Turner ◽  
Weiguang Zeng ◽  
David C. Jackson
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Soluble Proteins ◽  
Antibody Responses

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 A Next Generation Bivalent Human Ad5 COVID-19 Vaccine Delivering Both Spike and Nucleocapsid Antigens Elicits Th1 Dominant CD4+, CD8+ T-cell and Neutralizing Antibody Responses

2020 ◽  
Author(s):  
Adrian Rice ◽  
Mohit Verma ◽  
Annie Shin ◽  
Lise Zakin ◽  
Peter Sieling ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
Immune Responses ◽  
Cd8 T Cell ◽  
Surface Expression ◽  
Antibody Responses ◽  
Cell Surface Expression ◽  
Clinical Testing ◽  
Next Generation ◽  
Cell Responses

ABSTRACTIn response to the health crisis presented by the COVID-19 pandemic, rapid development of safe and effective vaccines that elicit durable immune responses is imperative. Recent reports have raised the concern that antibodies in COVID-19 convalescent patients may not be long lasting and thus even these individuals may require vaccination. Vaccine candidates currently in clinical testing have focused on the SARS-CoV-2 wild type spike (S) protein (S-WT) as the major antigen of choice and while pre-clinical and early clinical testing have shown that S elicits an antibody response, we believe the optimal vaccine candidate should be capable of inducing robust, durable T-cell responses as well as humoral responses. We report here on a next generation bivalent human adenovirus serotype 5 (hAd5) vaccine capable of inducing immunity in patients with pre-existing adenovirus immunity, comprising both an S sequence optimized for cell surface expression (S-Fusion) and a conserved nucleocapsid (N) antigen designed to be transported to the endosomal subcellular compartment, with the potential to generate durable immune protection. Our studies suggest that this bivalent vaccine is optimized for immunogenicity as evidenced by the following findings: (i) The optimized S-Fusion displayed improved S receptor binding domain (RBD) cell surface expression compared to S-WT where little surface expression was detected; (ii) the expressed RBD from S-Fusion retained conformational integrity and recognition by ACE2-Fc; (iii) the viral N protein modified with an enhanced T-cell stimulation domain (ETSD) localized to endosomal/lysosomal subcellular compartments for MHC I/II presentation; and (iv) these optimizations to S and N (S-Fusion and N-ETSD) generated enhanced de novo antigen-specific B cell and CD4+ and CD8+ T-cell responses in antigen-naive pre-clinical models. Both the T-cell and antibody immune responses to S and N demonstrated a T-helper 1 (Th1) bias. The antibody responses were neutralizing as demonstrated by two independent SARS-CoV-2 neutralization assays. Based on these findings, we are advancing this next generation bivalent hAd5 S-Fusion + N-ETSD vaccine as our lead clinical candidate to test for its ability to provide robust, durable cell-mediated and humoral immunity against SARS-CoV-2 infection. Further studies are ongoing to explore utilizing this vaccine construct in oral, intranasal, and sublingual formulations to induce mucosal immunity in addition to cell-mediated and humoral immunity. The ultimate goal of an ideal COVID-19 vaccine is to generate long-term T and B cell memory.

Primary immune responses to human CMV: a critical role for IFN-γ–producing CD4+ T cells in protection against CMV disease

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2686-2692 ◽  
Author(s):  
Laila E. Gamadia ◽  
Ester B. M. Remmerswaal ◽  
Jan F. Weel ◽  
Frederieke Bemelman ◽  
René A. W. van Lier ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Effector Memory

The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)–specific CD4+ and CD8+ T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8+ cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA−CD27+CCR7− CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4+ T-cell response preceded CMV-specific CD8+T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4+ T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8+ T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4+ T cells is necessary for recovery of infection.

scholarly journals Author response: Squalene emulsion-based vaccine adjuvants stimulate CD8 T cell, but not antibody responses, through a RIPK3-dependent pathway

2020 ◽  
Author(s):  
Eui Ho Kim ◽  
Matthew C Woodruff ◽  
Lilit Grigoryan ◽  
Barbara Maier ◽  
Song Hee Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Antibody Responses ◽  
Author Response ◽  
Vaccine Adjuvants ◽  
Dependent Pathway

scholarly journals Immunization with a Mixture of HIV Env DNA and VLP Vaccines Augments Induction of CD8 T Cell Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Ling Ye ◽  
Zhiyuan Wen ◽  
Ke Dong ◽  
Lei Pan ◽  
Zhigao Bu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Dna Vaccine ◽  
Cell Response ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Antibody Responses ◽  
Cell Responses ◽  
Virus Like Particle

The immune response induced by immunization with HIV Env DNA and virus-like particle (VLP) vaccines was investigated. Immunization with the HIV Env DNA vaccine induced a strong CD8 T cell response but relatively weak antibody response against the HIV Env whereas immunization with VLPs induced higher levels of antibody responses but little CD8 T cell response. Interestingly, immunization with a mixture the HIV Env DNA and VLP vaccines induced enhanced CD8 T cell and antibody responses. Further, it was observed that the mixing of DNA and VLP vaccines during immunization is necessary for augmenting induction of CD8 T cell responses and such augmentation of CD8 T cell responses was also observed by mixing the HIV Env DNA vaccine with control VLPs. These results show that immunization with a mixture of DNA and VLP vaccines combines advantages of both vaccine platforms for eliciting high levels of both antibody and CD8 T cell responses.

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.

scholarly journals Chimeric Murine Polyomavirus Virus-Like Particles Induce Plasmodium Antigen-Specific CD8+ T Cell and Antibody Responses

2019 ◽  
Vol 9 ◽  
Author(s):  
David J. Pattinson ◽  
Simon H. Apte ◽  
Nani Wibowo ◽  
Yap P. Chuan ◽  
Tania Rivera-Hernandez ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Antibody Responses ◽  
Virus Like Particles ◽  
Murine Polyomavirus

scholarly journals Squalene emulsion-based vaccine adjuvants stimulate CD8 T cell, but not antibody responses, through a RIPK3-dependent pathway

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Eui Ho Kim ◽  
Matthew C Woodruff ◽  
Lilit Grigoryan ◽  
Barbara Maier ◽  
Song Hee Lee ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Antibody Responses ◽  
Lymphoid Tissues ◽  
Soluble Antigen ◽  
Vaccine Adjuvants ◽  
Water Emulsion ◽  
Cell Responses ◽  
Deficient Mice

The squalene-based oil-in-water emulsion (SE) vaccine adjuvant MF59 has been administered to more than 100 million people in more than 30 countries, in both seasonal and pandemic influenza vaccines. Despite its wide use and efficacy, its mechanisms of action remain unclear. In this study we demonstrate that immunization of mice with MF59 or its mimetic AddaVax (AV) plus soluble antigen results in robust antigen-specific antibody and CD8 T cell responses in lymph nodes and non-lymphoid tissues. Immunization triggered rapid RIPK3-kinase dependent necroptosis in the lymph node which peaked at 6 hr, followed by a sequential wave of apoptosis. Immunization with alum plus antigen did not induce RIPK3-dependent signaling. RIPK3-dependent signaling induced by MF59 or AV was essential for cross-presentation of antigen to CD8 T cells by Batf3-dependent CD8+ DCs. Consistent with this, RIPK3 deficient or Batf3 deficient mice were impaired in their ability to mount adjuvant-enhanced CD8 T cell responses. However, CD8 T cell responses were unaffected in mice deficient in MLKL, a downstream mediator of necroptosis. Surprisingly, antibody responses were unaffected in RIPK3-kinase or Batf3 deficient mice. In contrast, antibody responses were impaired by in vivo administration of the pan-caspase inhibitor Z-VAD-FMK, but normal in caspase-1 deficient mice, suggesting a contribution from apoptotic caspases, in the induction of antibody responses. These results demonstrate that squalene emulsion-based vaccine adjuvants induce antigen-specific CD8 T cell and antibody responses, through RIPK3-dependent and-independent pathways, respectively.

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