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High Prevalence of Neutralizing Activity against Multiple Unrelated HIV-1 Subtype B Variants in Sera from HIV-1 Subtype B Infected Individuals: Evidence for Subtype Specific Rather than Strain Specific Neutralizing Activity

¹ Academic Medical Center, Amsterdam;
² Monogram Biosciences

³ E-mail: h.schuitemaker{at}amc.uva.nl

It is assumed that an effective HIV-1 vaccine should be capable of eliciting neutralizing antibodies. However, even the best antibodies known to date lack neutralizing ability against a significant proportion of primary HIV-1 variants and despite great efforts, still no immunogen is available that can elicit humoral immunity that can protect against infection or disease progression.We tested sera from 35 participants from the Amsterdam Cohort Studies on HIV-1 infection, who were all infected with HIV-1 subtype B and therapy naive at the time of sampling, for neutralizing activity against a panel of 23 tier 2-3 HIV-1 variants, with a minimum of 5 HIV-1 variants per subtype A, B, C and D. Strong cross-clade neutralizing activity was detected in sera from 7 individuals. Strikingly, sera from 22 out of 35 individuals (63%) neutralized 3 or more of the 6 tier 2-3 HIV-1 subtype B viruses in the panel. There was a strong correlation between neutralization titer and breadth in serum. Indeed, the IC50 of sera with strong cross-clade neutralizing activity was significantly higher than the IC50 of sera with cross-subtype B activity, which in turn had a higher IC50 than sera with the lowest neutralization breadth.These results imply that humoral immunity, at least in HIV-1 subtype B infected individuals, is often subtype-specific rather than strain-specific and that the breadth of neutralization is correlated with the titer of neutralizing activity in serum. Considering the difficulties in designing a vaccine that is capable of eliciting cross-clade neutralizing activity, subtype-specific vaccines may be explored as an interesting alternative.

Received 7 August 2009; accepted 25 September 2009.