Natural Immune Response to HIV Not Sufficient to Prevent Secondary Superinfection

Researchers studying the phenomenon known as HIV superinfection have determined that the immune system's initial antibody response may not be sufficient to provide protection against later infection with a different HIV virus, a finding that may have significant implications for HIV vaccine development. They report their findings in the December 2008 issue of the Journal of Virology.

HIV superinfection is a condition in which a person with established human immunodeficiency virus infection acquires a second strain of the virus. Superinfection is not the same as co-infection, where an individual becomes infected with two different viruses at the same time. Recent studies suggest that as many as 5 percent of HIV-patients may become superinfected, however it is unclear whether superinfection only occurs in individuals with particularly poor immune responses or whether immune responses during HIV-1 infection are in general inadequate to prevent infection.

Scientists from the FredHutchinsonCancerResearchCenter and the University of Washington, Seattle compared the levels of HIV-1-specific neutralizing antibodies (NAbs) in six women superinfected between one to five years after initial infection to those of 18 control subjects with similar risk factors. No significant differences in the breadth or potency of NAb responses were observed just prior to the second infection. In fact, four of the six patients had relatively broad and potent NAb responses prior to superinfection. Additional analysis of the superinfecting virus variants showed no inherent resistance to antibody neutralization.

The fact that the superinfected individuals had NAbs that could neutralize the superinfecting strains led the researchers to believe that the level of NAbs elicited during natural HIV infection may not be sufficient to block HIV infection.

"An effective HIV-1 vaccine will therefore need to elicit more robust NAb responses than found during natural infection," say the researchers. "Indeed, this is the case for some other viral vaccines, such as those for hepatitis B and human papillomavirus, which elicit equivalent or higher levels of NAbs than natural infection."

Reference: C.A. Blish, O.C. Dogan, N.R. Derby, M. Nguyen, B. Chohan, B.A. Richardson, J. Overbaugh. 2008. Human immunodeficiency virus type 1 superinfection occurs despite relatively robust neutralizing antibody responses. Journal of Virology, 82. 24: 12094-12103.