The current study assessed the immunogenicity and protective efficacy of various prime-boost
vaccine regimens in rhesus macaques using combinations of
recombinant DNA (
rDNA), recombinant MVA (rMVA), and subunit
gp140 protein. The
rDNA and rMVA vectors were constructed to express Env from HIV-1 subtype CRF01_AE and Gag-Pol from CRF01_AE or SIVmac 239. One of the rMVAs, MVA/CMDR, has been recently tested in humans. Immunizations were administered at months 0 and 1 (prime) and months 3 and 6 (boost). After priming, HIV env-specific serum
IgG was detected in monkeys receiving
gp140 alone or rMVA but not in those receiving
rDNA. Titers were enhanced in these groups after boosting either with
gp140 alone or with rMVA plus
gp140. The groups that received the
rDNA prime developed env-specific
IgG after boosting with rMVA with or without
gp140. HIV Env-specific serum
IgG binding
antibodies were elicited more frequently and of higher titer, and breadth of
neutralizing antibodies was increased with the inclusion of the subunit Env boost. T cell responses were measured by tetramer binding to Gag p11c in Mamu-A*01 macaques, and by IFN-γ ELISPOT assay to SIV-Gag. T cell responses were induced after vaccination with the highest responses seen in macaques immunized with
rDNA and rMVA. Macaques were challenged intravenously with a novel SHIV-E virus (SIVmac239 Gag-Pol with an HIV-1 subtype E-Env CAR402). Post challenge with SHIV-E, antibody titers were boosted in all groups and peaked at 4 weeks. Robust T cell responses were seen in all groups post challenge and in macaques immunized with
rDNA and rMVA a clear boosting of responses was seen. A greater than two-log drop in
RNA copies/ml at peak
viremia and earlier set point was achieved in macaques primed with
rDNA, and boosted with rMVA/SHIV-AE plus
gp140. Post challenge
viremia in macaques immunized with other regimens was not significantly different to that of controls. These results demonstrate that a
gp140 subunit and inclusion of SIV Gag-Pol may be critical for control of SHIV post challenge.