Measuring human T cell responses in blood and gut samples using qualified methods suitable for evaluation of HIV vaccine candidates in clinical trials

2011 ◽  
Vol 370 (1-2) ◽  
pp. 43-54 ◽  
Author(s):  
Harry Kaltsidis ◽  
Hannah Cheeseman ◽  
Jakub Kopycinski ◽  
Ambreen Ashraf ◽  
Michelle Cashin Cox ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
T Cell Responses ◽  
Hiv Vaccine ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Human T Cell

scholarly journals Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

2016 ◽  
Vol 90 (8) ◽  
pp. 4133-4149 ◽  
Author(s):  
Benedikt Asbach ◽  
Alexander Kliche ◽  
Josef Köstler ◽  
Beatriz Perdiguero ◽  
Mariano Esteban ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Immune Responses ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Hiv Vaccine ◽  
The Novel ◽  
Cell Responses ◽  
Protein Boost ◽  
Clade C

ABSTRACTIn a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8+and CD4+T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings.IMPORTANCEWithin the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols.

scholarly journals A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 181 ◽  
Author(s):  
Gabriela Tapia-Calle ◽  
Philip A. Born ◽  
Georgia Koutsoumpli ◽  
Martin Ignacio Gonzalez-Rodriguez ◽  
Wouter L. J. Hinrichs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Animal Models ◽  
Vaccine Development ◽  
Animal Experiments ◽  
T Cell Responses ◽  
T Cell Subsets ◽  
Vaccine Candidates ◽  
Cell Responses

Vaccine development is an expensive and time-consuming process that heavily relies on animal models. Yet, vaccine candidates that have previously succeeded in animal experiments often fail in clinical trials questioning the predictive value of animal models. Alternative assay systems that can add to the screening and evaluation of functional characteristics of vaccines in a human context before embarking on costly clinical trials are therefore urgently needed. In this study, we have established an in vitro system consisting of long-term cultures of unfractionated peripheral blood mononuclear cells (PBMCs) from healthy volunteers to assess (recall) T cell responses to vaccine candidates. We observed that different types of influenza vaccines (whole inactivated virus (WIV), split, and peptide vaccines) were all able to stimulate CD4 and CD8 T cell responses but to different extents in line with their reported in vivo properties. In-depth analyses of different T cell subsets revealed that the tested vaccines evoked mainly recall responses as indicated by the fact that the vast majority of the responding T cells had a memory phenotype. Furthermore, we observed vaccine-induced activation of T follicular helper cells, which are associated with the induction of humoral immune responses. Our results demonstrate the suitability of the established PBMC-based system for the in vitro evaluation of memory T cell responses to vaccines and the comparison of vaccine candidates in a human immune cell context. As such, it can help to bridge the gap between animal experiments and clinical trials and assist in the selection of promising vaccine candidates, at least for recall antigens.

Human T-cell responses to oral streptococci in human PBMC-NOD/SCID mice

2006 ◽  
Vol 21 (3) ◽  
pp. 169-176 ◽  
Author(s):  
M. A. Salam ◽  
R. Nakao ◽  
H. Yonezawa ◽  
H Watanabe ◽  
H. Senpuku
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Scid Mice ◽  
Oral Streptococci ◽  
Human Pbmc ◽  
Cell Responses ◽  
Human T Cell

scholarly journals Human T cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells

2001 ◽  
Vol 94 (6) ◽  
pp. 807-812 ◽  
Author(s):  
Emma J. Davidson ◽  
Michael D. Brown ◽  
Deborah J. Burt ◽  
Joanna L. Parish ◽  
Kevin Gaston ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Hpv 16 ◽  
Cell Responses ◽  
Human T Cell

scholarly journals Early CD4+ T Cell Responses Are Associated with Subsequent CD8+ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0152952 ◽  
Author(s):  
Edouard Lhomme ◽  
Laura Richert ◽  
Zoe Moodie ◽  
Chloé Pasin ◽  
Spyros A. Kalams ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Hiv Vaccine ◽  
Cd4 T Cell ◽  
Vaccine Strategy ◽  
Cell Responses

Human T cell responses to the antigen ESAT-6 characterize vaccine candidate and potential diagnostic test for tuberculosis

1999 ◽  
Vol 39 (1) ◽  
pp. A9
Author(s):  
A. Lalvani ◽  
A. Pathan ◽  
R. Brookes ◽  
H. Pritchard ◽  
R. Wilkinson ◽  
...  
Keyword(s):  
T Cell ◽  
Diagnostic Test ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Cell

Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of simian virus 40 large T antigen

2001 ◽  
Vol 82 (1) ◽  
pp. 155-162 ◽  
Author(s):  
Markwin P. Velders ◽  
M. Fatima Macedo ◽  
Maurizio Provenzano ◽  
Amira G. Elmishad ◽  
Hermann-Georg Holzhütter ◽  
...  
Keyword(s):  
T Cell ◽  
Simian Virus 40 ◽  
T Cell Responses ◽  
Simian Virus ◽  
T Antigen ◽  
Large T Antigen ◽  
Cell Responses ◽  
Human T Cell

Enhancement of human T cell responses to allogeneic stimuli by factor VIII concentrates

1992 ◽  
Vol 82 (1) ◽  
pp. 94-98 ◽  
Author(s):  
Alison Batchelor ◽  
C. Michael Steel ◽  
Christopher A. Ludlam
Keyword(s):  
T Cell ◽  
Factor Viii ◽  
T Cell Responses ◽  
Cell Responses ◽  
Human T Cell ◽  
Factor Viii Concentrates
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