[MoOrA1091] Whole inactivated virion SIV vaccine with functional envelope glycoproteins: Immunogenicity and protective efficacy

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Whole inactivated virion SIV vaccine with functional envelope glycoproteins: Immunogenicity and protective efficacy

[AUTHOR(S):] J.D. Lifson¹

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1091

BACKGROUND: We used a novel chemical inactivation method to produce non-infectious SIV virions with functional envelope glycoproteins. We tested the immunogenicity and protective efficacy of this immunogen, with and without CpG motif containing immunostimulatory oligodeoxynucleotides (ISS ODN), in the rhesus/SIVmac239 challenge model.

METHODS: Inactivated virions were prepared from a SIVmac239 derived virus. 8 rhesus macaques were immunized with inactivated virus (weeks 0,4,8,24; IM and ID). 4 of the 8 animals received injections of ISS ODN at the same sites, 24 hrs before each immunization. 2 naïve animals, and 4 animals immunized with microvesicles containing host cell antigens but no viral antigens (2 with ISS ODN, 2 without) were controls. Anti-SIV Ab and CMI responses were monitored. Animals were challenged (30 MID50 IV of SIVmac239) 4 weeks after the final boost; plasma viral load was followed.

RESULTS: All SIV immunized animals developed anti-SIV binding Ab; SIVmac239 neutralizing Ab (1:20-1:40) was detected transiently in 3/4 virus/ISS ODN immunized animals. IFN-γ ELISPOT responses by CD8+ cells demonstrated in vivo cross priming. On challenge all controls and 7/8 virus immunized animals became demonstrably infected; early viral loads were lower in SIV vaccinees than controls (p = 0.0066 at wk 2 and p = 0.02 at wk 4; Wilcoxon rank-sum test). The virus/ISS ODN immunized animal with the highest DOC ELISPOT frequency has maintained plasma SIV RNA levels < 100 copy Eq/mL and negative PBMC virus rescue cultures.

CONCLUSIONS: The vaccine was safe and immunogenic and generated CD8+ T cell responses in vivo. 1/4 virus/ISS ODN macaques showed apparently solid protection against an extremely rigorous IV challenge, suggesting the strategy merits further evaluation. With further optimization this may be a useful component of vaccine approaches for the prevention of AIDS.

Presenting author: Jeffrey Lifson

1SAIC Frederick, NCI, AIDS Vaccine Program/SAIC Frederick, National Cancer Institute at Frederick, Building 535, Fifth Floor, Frederick, MD 21702, United States.

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