CD8(+) lymphocyte antiviral activity in monkeys immunized with SIV recombinant poxvirus vaccines: Potential role in vaccine efficacy

Protection against intravenous sinian immunodeficiency virus (SIV) challeng e was assessed in rhesus macaques after immunization with a highly attenuat ed vaccinia (NYVAC)-SIV recombinant. One-third of vaccinated animals contro lled viral infection and progressed to disease more slowly than control ani mals (Benson J, et al.: J Virol 1998;72:4170). However, this protection was not associated with neutralizing antibodies, cytotoxic T lymphocytes, or h elper T cell responses. To explore other potential correlates of protection , me examined CD8(+) T cell antiviral activity in macaques vaccinated with NYVAC-SIV, with or without added cytokine adjuvants, and in controls receiv ing only IL-12 or IL-12 plus IL-2. Before immunization, naive macaques exhi bited a broad range of CD8(+) T cell antiviral activity. Nevertheless, in t he course of immunization, the vaccinated macaques as a group developed inc reased CD8(+) T cell antiviral activity while the controls remained stable. Infectious SIV exposure also increased antiviral activity. Prechallenge an tiviral activity levels of vaccinated macaques were not sufficient to preve nt SN transmission or control viral replication during acute infection. How ever, vaccinated animals consistently exhibited reduced viral loads postcha llenge compared with controls. Moreover, high suppressive activity 8 weeks postchallenge, at which time the viremia set point was established, was sig nificantly correlated with reduced viral load and slow disease progression. Prechallenge antiviral activity influenced this result, as decreased virem ia and slow progressor status were more apparent in macaques with high supp ressive activity both pre- and postchallenge. Our data demonstrate the impa ct of CD8(+) antiviral activity on viral replication and disease progressio n, and suggest that vaccine designs able to elicit high levels of this acti vity will contribute significantly to protective efficacy.