HIV This Week

Blish CA, Dogan OC, Derby NR, Nguyen MA, Chohan B, Richardson BA, Overbaugh J. HIV-1 Superinfection Occurs Despite Relatively Robust Neutralizing Antibody Responses. J Virol. 2008;82(24):12094-103.

Superinfection by a second HIV-1 strain indicates that gaps in protective immunity occur during natural infection. To define the role of HIV-1-specific neutralizing antibodies in this setting, Blish and colleagues examined neutralizing antibody responses in 6 women who became superinfected between approximately 1-5 years following initial infection compared to 18 women with similar risk factors who did not. Although superinfected individuals had less neutralizing antibody breadth than did matched controls at approximately 1 year post-infection, no significant differences in the breadth or potency of neutralizing antibody responses were observed just prior to the second infection. In fact, four of the six subjects had relatively broad and potent neutralizing antibody responses prior to infection by the second strain. To more specifically examine the specificity of the neutralizing antibodies against the superinfecting virus, these variants were cloned from five of the six individuals. The superinfecting variants did not appear to be inherently neutralization resistant, as measured against a pool of plasma from unrelated HIV-infected individuals. Moreover, the superinfected individuals were able to mount autologous neutralizing antibody responses to these variants following re-infection. In addition, most superinfected individuals had neutralizing antibodies that could neutralize their second viral strains prior to their re-infection, suggesting that the level of neutralizing antibodies elicited during natural infection was not sufficient to block infection. These data indicate that preventing infection by vaccination will likely require broader and more potent neutralizing antibody responses than those found in HIV-1 infected individuals.

Editors’ note: Superinfection can occur in the first year following initial infection when immune responses to HIV may not be fully mature or during chronic infection when they should be fully developed. It is unknown whether individuals who acquire a second HIV infection are a subset of people with particularly poor immune responses or whether normal immune responses to HIV are inadequate to prevent superinfection. This small study suggests the latter, i.e. the levels of neutralizing antibodies to susceptible virus were inadequate to prevent superinfection. As is the case for hepatitis B and human papilloma virus, it appears that an HIV-1 vaccine will need to elicit more robust neutralising antibody responses than those found during natural infection.