J Virol. 2016 Mar 28; 90(8):4133-49.

PubMed ID: 26865719

Potential to streamline heterologous DNA prime and NYVAC/protein boost HIV vaccine regimens in rhesus macaques by employing improved antigens

Asbach B, Kliche A, Köstler J, Perdiguero B, Esteban M, Jacobs BL, Montefiori DC, LaBranche CC, Yates NL, Tomaras GD, Ferrari G, Foulds KE, Roederer M, Landucci G, Forthal DN, Seaman MS, Hawkins N, Self SG, Sato A, Gottardo R, Phogat S, Tartaglia J, Barnett SW, Burke B, Cristillo AD, Weiss DE, Francis J, Galmin L, Ding S, Heeney JL, Pantaleo G, Wagner R

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.