Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens.
Abstract
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.
Type
Journal articleSubject
AIDS VaccinesAnimals
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
Permalink
https://hdl.handle.net/10161/11663Published Version (Please cite this version)
10.1128/JVI.03135-15Publication Info
Asbach, Benedikt; Kliche, Alexander; Köstler, Josef; Perdiguero, Beatriz; Esteban,
Mariano; Jacobs, Bertram L; ... Wagner, Ralf (2016). Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine
Regimens in Rhesus Macaques by Employing Improved Antigens. J Virol, 90(8). pp. 4133-4149. 10.1128/JVI.03135-15. Retrieved from https://hdl.handle.net/10161/11663.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Guido Ferrari
Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research
and immune monitoring studies. The research revolves around three main areas of interest:
class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity
(ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With
continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation
along with many other productive collaborations wi
Celia Crane LaBranche
Associate Professor Emeritus
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research
and Development in the Department of Surgery, Division of Surgical Sciences, Duke
University Medical Center. His major research interests are viral immunology and AIDS
vaccine development, with a special emphasis on neutralizing antibodies. One of his
highest priorities is to identify immunogens that generate broadly cross-reactive
neutralizing antibodies for inclusion in HIV vaccines. Many aspects of the
Georgia Doris Tomaras
Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor
of Molecular Genetics and Microbiology and is a Fellow of the American Academy of
Microbiology (AAM) and a Fellow of the American Association for the Advancement of
Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology
(CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her
national and international leadership roles i
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info