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

Details

Serval ID
serval:BIB_C0177FF88AB3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens.
Journal
Journal of virology
Author(s)
Asbach B., Kliche A., Köstler J., Perdiguero B., Esteban M., Jacobs B.L., Montefiori D.C., LaBranche C.C., Yates N.L., Tomaras G.D., Ferrari G., Foulds K.E., Roederer M., Landucci G., Forthal D.N., Seaman M.S., Hawkins N., Self S.G., Sato A., Gottardo R., Phogat S., Tartaglia J., Barnett S.W., Burke B., Cristillo A.D., Weiss D.E., Francis J., Galmin L., Ding S., Heeney J.L., Pantaleo G., Wagner R.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
04/2016
Peer-reviewed
Oui
Volume
90
Number
8
Pages
4133-4149
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
In 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.
Within 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.
Keywords
AIDS Vaccines/genetics, AIDS Vaccines/immunology, Animals, Antibodies, Neutralizing/immunology, Antibody-Dependent Cell Cytotoxicity, DNA Primers, HIV Antibodies/immunology, HIV Antigens/immunology, HIV-1/immunology, Interferon-gamma/biosynthesis, Male, T-Lymphocytes/immunology, Vaccination/methods, Vaccines, DNA/genetics, Vaccines, DNA/immunology, gag Gene Products, Human Immunodeficiency Virus/genetics, gag Gene Products, Human Immunodeficiency Virus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
20/02/2016 17:09
Last modification date
01/03/2022 6:37
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