scholarly journals DNA plasmid HIV vaccine design, number of doses, participant gender, and body mass index affect T-cell responses across HIV vaccine clinical trials

Retrovirology ◽  
2012 ◽  
Vol 9 (S2) ◽  
Author(s):  
C Morgan ◽  
X Jin ◽  
X Yu ◽  
S De Rosa ◽  
J Kublin ◽  
...  
2016 ◽  
Vol 90 (8) ◽  
pp. 4133-4149 ◽  
Author(s):  
Benedikt Asbach ◽  
Alexander Kliche ◽  
Josef Köstler ◽  
Beatriz Perdiguero ◽  
Mariano Esteban ◽  
...  

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.


2011 ◽  
Vol 370 (1-2) ◽  
pp. 43-54 ◽  
Author(s):  
Harry Kaltsidis ◽  
Hannah Cheeseman ◽  
Jakub Kopycinski ◽  
Ambreen Ashraf ◽  
Michelle Cashin Cox ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0152952 ◽  
Author(s):  
Edouard Lhomme ◽  
Laura Richert ◽  
Zoe Moodie ◽  
Chloé Pasin ◽  
Spyros A. Kalams ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14295-e14295 ◽  
Author(s):  
Eniko Rita Toke ◽  
Mónika Megyesi ◽  
Levente Molnar ◽  
József Tóth ◽  
Orsolya Lőrincz ◽  
...  

e14295 Background: Neoantigen vaccines can activate T-cells that specifically kill tumor cells. However, most vaccine peptides, selected either as HLA-binders or as HLA-presented epitopes, do not induce T-cell responses in HLA allele-matched individuals. We hypothesized that personal-epitopes (PEPIs) binding to multiple autologous HLA-alleles induce potent T-cell responses. Methods: Epitopes binding to single HLA and PEPIs binding to 3 autologous HLA-alleles were identified with our novel and validated PEPI Test (CE Marked) and correlated with CD8+ and CD4+ T-cell responses of (pre)malignant patients vaccinated with Synthetic Long Peptides (SLPs) in 2 clinical trials. A Model Population of 433 HLA-genotyped individuals was used to determine the percentage of subjects with PEPIs from SLPs (PEPI-Score). As a proof of principle, a personal vaccine was developed matching with 14 HLA-alleles of a cancer patient with PEPIs from 12 tumor-antigens. T-cell reactivities were tested by interferon-γ ELISPOT. Results: There was no correlation between single HLA-binding epitopes and HPV-specific T-cell responses of patients. In contrast, there was 90% and 69% agreement between HLA-class-I PEPIs and CD8+ T-cell responses (p < 0.001) and HLA-class-II PEPIs and CD4+ T-cell responses (p = 0.005), respectively. PEPI-Score predicted the T-cell response rate of SLP vaccine clinical trials. As predicted by the PEPI Test, personal vaccine treatment activated tumor-specific T-cells: 91% and 100% of the vaccine peptides elicited CD8+ and CD4+ T-cell responses, respectively. Conclusions: A patient’s HLA genotype is a major determinant of vaccine responses and PEPIs are genetic biomarkers of T-cell responses. PEPI Test prediction of vaccine responses can be utilized by clinicians for selecting the vaccine treatment and for the development of highly immunogenic personal vaccines matched to a patient’s complete HLA genotype (NCT03391232).


Vaccine ◽  
2021 ◽  
Author(s):  
Susan Pereira Ribeiro ◽  
Vania Gomes De Moura Mattaraia ◽  
Rafael Ribeiro Almeida ◽  
Elizabeth Juliana Ghiuro Valentine ◽  
Natiely Silva Sales ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76215 ◽  
Author(s):  
Sarah Kutscher ◽  
Claudia J. Dembek ◽  
Simone Deckert ◽  
Carolina Russo ◽  
Nina Körber ◽  
...  

2019 ◽  
Vol 13 ◽  
pp. 253-264 ◽  
Author(s):  
Esther Broset ◽  
Narcís Saubi ◽  
Núria Guitart ◽  
Nacho Aguilo ◽  
Santiago Uranga ◽  
...  

2011 ◽  
Vol 187 (8) ◽  
pp. 4268-4279 ◽  
Author(s):  
Daniela Weiskopf ◽  
Lauren E. Yauch ◽  
Michael A. Angelo ◽  
Daisy V. John ◽  
Jason A. Greenbaum ◽  
...  

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