scholarly journals The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques—implications for recombinant vaccine design

2010 ◽  
Vol 62 (9) ◽  
pp. 593-600 ◽  
Author(s):  
Philip A. Mudd ◽  
Shari M. Piaskowski ◽  
Patricia C. Costa Neves ◽  
Richard Rudersdorf ◽  
Holly L. Kolar ◽  
...  
Keyword(s):  
T Cell ◽  
Yellow Fever ◽  
Rhesus Macaques ◽  
Vaccine Design ◽  
T Cell Responses ◽  
Viral Proteins ◽  
Recombinant Vaccine ◽  
Yellow Fever Vaccine ◽  
Cell Responses

scholarly journals CD8 T cell responses to live, viral Yellow fever vaccine in humans

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Rama Akondy ◽  
Joseph Miller ◽  
Nathan Monson ◽  
Hong Wu ◽  
Farah Quyyumi ◽  
...  
Keyword(s):  
T Cell ◽  
Yellow Fever ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Yellow Fever Vaccine ◽  
Cell Responses

scholarly journals CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5–7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

Vaccine ◽  
2010 ◽  
Vol 28 (51) ◽  
pp. 8183-8188 ◽  
Author(s):  
Patrícia C.C. Neves ◽  
Richard A. Rudersdorf ◽  
Ricardo Galler ◽  
Myrna C. Bonaldo ◽  
Marlon Gilsepp Veloso de Santana ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Gamma Delta ◽  
Cell Responses ◽  
Ifn Γ ◽  
Yellow Fever Vaccination

scholarly journals Recombinant Yellow Fever Vaccine Virus 17D Expressing Simian Immunodeficiency Virus SIVmac239 Gag Induces SIV-Specific CD8+ T-Cell Responses in Rhesus Macaques

2010 ◽  
Vol 84 (7) ◽  
pp. 3699-3706 ◽  
Author(s):  
Myrna C. Bonaldo ◽  
Mauricio A. Martins ◽  
Richard Rudersdorf ◽  
Philip A. Mudd ◽  
Jonah B. Sacha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Yellow Fever ◽  
T Cell Responses ◽  
Vaccine Virus ◽  
Yellow Fever Vaccine ◽  
Effector Memory ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Here we describe a novel vaccine vector for expressing human immunodeficiency virus (HIV) antigens. We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8+ T-cell responses in the rhesus macaque. Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8+ T-cell responses after recombinant YF17D boosting. These recombinant YF17D-induced SIV-specific CD8+ T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4+ T cells.

scholarly journals Novel Recombinant Mycobacterium bovis BCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques

2010 ◽  
Vol 84 (12) ◽  
pp. 5898-5908 ◽  
Author(s):  
Maximillian Rosario ◽  
Richard Hopkins ◽  
John Fulkerson ◽  
Nicola Borthwick ◽  
Máire F. Quigley ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Mycobacterium Bovis ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.

CpG oligonucleotides induce strong humoral but only weak CD4+ T cell responses to protein antigens in rhesus macaques in vivo

Vaccine ◽  
2005 ◽  
Vol 23 (25) ◽  
pp. 3310-3317 ◽  
Author(s):  
Gunther Hartmann ◽  
Anja Marschner ◽  
Pablo Renner Viveros ◽  
Christiane Stahl-Hennig ◽  
Martin Eisenblätter ◽  
...  
Keyword(s):  
T Cell ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Protein Antigens ◽  
Cell Responses ◽  
Cpg Oligonucleotides

CpG pretreatment enhances antiviral T-cell immunity against cytomegalovirus

Blood ◽  
2013 ◽  
Vol 122 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Monique L. Ong ◽  
Matthew E. Wikstrom ◽  
Peter Fleming ◽  
Marie J. Estcourt ◽  
Paul J. Hertzog ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Viral Proteins ◽  
T Cell Immunity ◽  
Cross Presentation ◽  
Cell Responses ◽  
Cell Immunity ◽  
Key Points

Key Points Fully functional CD8 T-cell responses, control of infection, and protection from organ pathology are attained without cross-presentation. Direct presentation generates responses that limit disease and ensure host survival despite the presence of immunomodulatory viral proteins.

scholarly journals HIV-Specific CD4 T Cell Responses to Different Viral Proteins Have Discordant Associations with Viral Load and Clinical Outcome

2011 ◽  
Vol 86 (1) ◽  
pp. 277-283 ◽  
Author(s):  
S. Ranasinghe ◽  
M. Flanders ◽  
S. Cutler ◽  
D. Z. Soghoian ◽  
M. Ghebremichael ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Clinical Outcome ◽  
T Cell Responses ◽  
Viral Proteins ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Alba Grifoni ◽  
Hannah Voic ◽  
Sandeep Kumar Dhanda ◽  
Conner K. Kidd ◽  
James D. Brien ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
Live Attenuated Vaccine ◽  
Cell Responses ◽  
Attenuated Vaccine ◽  
E Protein

ABSTRACT Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases >1,000-fold-lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species. IMPORTANCE The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the nonstructural (NS) and capsid (C) antigens, which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses among different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses and might thus impair vaccine performance.

scholarly journals 2729. mRNA Vaccines Encoding Conserved Influenza Antigens Induce Robust and Durable Immunity in Rhesus Macaques

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S961-S961
Author(s):  
Jessica Flynn ◽  
Kara Cox ◽  
Sinoeun Touch ◽  
Yangsi Ou ◽  
Teresa Weber ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Rhesus Macaques ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Immune Recognition ◽  
Serum Antibodies ◽  
Ifn Gamma ◽  
Cell Responses ◽  
Lipid Nanoparticle

Abstract Background In response to immune pressure, influenza virus evolves, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response that can recognize multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the immunogenicity of mRNA vaccines encoding the stem domain of hemagglutinin (HA) or nucleoprotein (NP) in nonhuman primates (NHPs). Methods Rhesus macaques were immunized three times intramuscularly, at 28 day intervals, with lipid nanoparticle-encapsulated mRNA encoding either HA stem (Yassine et al, 2015) or NP. Serum and PBMCs were collected up to 14 or 24 weeks, respectively, after the last vaccination. The magnitude and durability of humoral and cell-mediated immunity were evaluated. ELISA, competition ELISA, an in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter bioassay, and microneutralization assays were used to characterize serum immune responses. Intracellular cytokine staining (IFN-gamma and IL-2) was used to assess antigen-specific T-cell responses. Results HA stem-immunized NHPs developed a robust anti-stem binding titer after a single vaccine dose, and after two doses, serum antibodies recognized several antigenically distinct Group 1 HA proteins. This broad antibody response persisted for at least 14 weeks post-dose 3 (PD3). Serum antibodies showed ADCC activity and competed with a well-characterized broadly neutralizing antibody, CR9114, for binding to HA stem; however, the polyclonal serum had only minimal activity against a panel of H1N1 viruses in a microneutralization assay. HA-specific CD4+ T-cell responses were detectable PD3. A robust antibody binding response was also detected in NP-vaccinated NHPs, and titers remained high for at least 14 weeks PD3. Additionally, these animals developed robust NP-specific T-cell responses that persisted for at least 24 weeks PD3. On average, 0.5% of CD4+ and 4% of CD8+ T cells produced IFN-gamma in response to NP peptide stimulation at the peak of the response, 2 weeks after the last vaccine dose was administered. Conclusion Lipid nanoparticle-encapsulated mRNA vaccines encoding conserved influenza antigens induce a robust and durable immune response in NHPs. Disclosures All authors: No reported disclosures.

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