Transfer of neutralizing IgG to macaques 6 h but not 24 h after SHIV infection confers sterilizing protection: implications for HIV-1 vaccine development

Abstract

Passive transfer of high-titered antiviral neutralizing IgG, known to confer sterilizing immunity in pig-tailed monkeys, has been used to determine how soon after virus exposure neutralizing antibodies (NAbs) must be present to block a simian immunodeficiency virus (SIV)/HIV chimeric virus infection. Sterilizing protection was achieved in three of four macaques receiving neutralizing IgG 6 h after intravenous SIV/HIV chimeric virus inoculation as monitored by PCR analyses of and attempted virus isolations from plasma, peripheral blood mononuclear cell, and lymph node specimens. In the fourth animal, the production of progeny virus was suppressed for >4 weeks. A delay in transferring NAbs until 24 h after virus challenge resulted in infection in two of two monkeys. These results suggest that even if a vaccine capable of eliciting broadly reactive NAbs against primary HIV-1 were at hand, the Abs generated must remain at, or rapidly achieve, high levels within a relatively short period after exposure to virus to prevent the establishment of a primate lentivirus infection.

Fig. 1.

Plasma viral RNA levels and PBMC-associated viral DNA loads in pig-tailed macaques challenged with SHIV_DH12 after the administration of neutralizing IgG at 6 or 24 h after virus inoculation. The number of SHIV_DH12 RNA copies in the plasma or PBMC-associated viral DNA was determined over a 4- to 7-month period by quantitative RT-PCR or DNA PCR, respectively. Control animals PT98P033 and PT98P056 received IgG prepared from an HIV-1-uninfected chimpanzee.

Fig. 2.

End-point titrations of plasma anti-SHIV NAbs at various times after virus challenge. Virus neutralizing activity in plasma was evaluated in quadruplicate cultures of MT-4 cells after a 1-h incubation of virus (75 TCID₅₀) with 3-fold serial dilutions of plasma as described (5, 9). The number above each bar indicates the calculated NAb titer.