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152 Immune Serum Transfers Protection Mediated by HIV-1 rgp120 against SHIV Challenge
N. Almond1, A. Wade-Evans1, E. J. Stott1, B. Walker1, R. Hull1, G. Voss2, S. Cayphas*2, and R. Stebbings1
1NIBSC, UK and 2GlaxoSmithKline, Rixensart, Belgium
Background: Recombinant HIV-1 envelope vaccines have proceeded furthest in clinical trials. However, without an understanding of the mechanism by which these vaccines protect, the success or failure of the current Phase III clinical trials cannot be fully determined. We have applied the SHIV macaque model to characterise the vaccine-induced protection that may be elicited by HIV-1 rgp120.
Methods and Results: Groups of 4 Macaca fascicularis received 100 mug of HIV-1W61Drgp120 administered subcutaneously with the adjuvant AS0-2 on 3 or 8 occasions. Four weeks after the final immunisation all 8 vaccinates were challenged intravenously with SHIVW61D, which expresses the homologous HIV-1 envelope as the vaccine, along with 4 challenge controls. Following challenge all 4 controls became infected, whereas no evidence of infection was detected in the 4 macaques that received 8 immunisations. Virus breakthrough was observed in 2 of the 4 macaques that received 3 immunisations. Immune serum collected prior to challenge from the vaccinates that received 8 immunisations was pooled and transferred to naïve macaques by intraperitoneal injection. Twenty-four hours later the 3 recipients of immune serum were challenged intravenously with SHIVW61D along with 4 naïve controls. Marked protection was observed.
Conclusions: Current studies are designed to characterise the breadth of protection and determine the key serological responses that mediate this vaccine protection. These data indicate that HIV-1 rgp120-based vaccines can protect against challenge with SHIV and this protection is mediated at least in part by serological responses induced by the vaccine.
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