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

Asbach, Benedikt

Kliche, Alexander

Köstler, Josef

Perdiguero, Beatriz

Esteban, Mariano

Jacobs, Bertram L

Montefiori, David C

LaBranche, Celia C

Yates, Nicole L

Tomaras, Georgia D

Ferrari, Guido

Foulds, Kathryn E

Roederer, Mario

Landucci, Gary

Forthal, Donald N

Seaman, Michael S

Hawkins, Natalie

Self, Steven G

Sato, Alicia

Gottardo, Raphael

Phogat, Sanjay

Tartaglia, James

Barnett, Susan W

Burke, Brian

Cristillo, Anthony D

Weiss, Deborah E

Francis, Jesse

Galmin, Lindsey

Ding, Song

Heeney, Jonathan L

Pantaleo, Giuseppe

Wagner, Ralf

Silvestri, G

United States

2016-03-01T14:13:07Z

2016-04

UNLABELLED: 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. IMPORTANCE: 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.

http://www.ncbi.nlm.nih.gov/pubmed/26865719

JVI.03135-15

1098-5514

https://hdl.handle.net/10161/11663

eng

American Society for Microbiology

J Virol

10.1128/JVI.03135-15

AIDS Vaccines

Animals

Antibodies, Neutralizing

Antibody-Dependent Cell Cytotoxicity

DNA Primers

HIV Antibodies

HIV Antigens

HIV-1

Interferon-gamma

Male

T-Lymphocytes

Vaccination

Vaccines, DNA

gag Gene Products, Human Immunodeficiency Virus

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

Journal article

Montefiori, David C|0000-0003-0856-6319

LaBranche, Celia C|0000-0002-6653-6655

Tomaras, Georgia D|0000-0001-8076-1931

Ferrari, Guido|0000-0001-7747-3349

http://www.ncbi.nlm.nih.gov/pubmed/26865719

4133

4149

8

Basic Science Departments

Clinical Science Departments

Duke

Duke Human Vaccine Institute

Global Health Institute

Immunology

Institutes and Centers

Institutes and Provost's Academic Units

Molecular Genetics and Microbiology

School of Medicine

Surgery

Surgery, Surgical Sciences

Surgery, Surgical Sciences Section for AIDS Research & Development

University Institutes and Centers

Published online

90