From the Journals

HIV superinfection: No boost to broadly neutralizing antibodies



Infection by a second HIV strain after established primary infection (HIV superinfection) has been associated with broader antibody production, and such events are analogous to heterologous prime-boost immunizations, according to a report published in Cell Host & Microbe.

Antibodies ©Svisio/Thinkstock

This phenomenon offers an opportunity to assess how the human immune system responds to sequential exposure to two distinct HIV envelope (Env) antigens, according to the authors, Daniel J. Sheward, a PhD student and scientific officer at the University of Cape Town, South Africa, and his colleagues.

Mr. Sheward and his colleagues followed 108 women recruited in acute/early infection and screened for superinfection over approximately 2 years in the Centre for the AIDS Programme of Research in South Africa (CAPRISA 002 cohort). In a previous study, they identified five superinfected participants, all of whom were superinfected between 3 and 10 months following primary infection. Only two of these patients developed antibodies capable of neutralizing heterologous viruses at 2 years, and one individual developed extremely potent broadly neutralizing antibodies (bnAbs). However, the contribution of superinfection itself to the development of antibody breadth in these individuals was not clear, prompting the current study (Cell Host Microbe. 2018 Oct 10;24[4]:593-9).

The researchers compared neutralization breadth (defined as the percent of heterologous viruses neutralized) present in plasma sampled 2 years post infection between the previously identified superinfected participants and the remaining CAPRISA 002 cohort participants. Four virus strains accounted for the superinfections. Antibody breadth was compared at 2 years post infection to four of the five of the superinfected participants, as they all had at least 2 years of antiretroviral-naive follow-up.

The researchers compared the peak neutralizing antibody (nAb) titers against all four superinfecting viruses with their matched primary infecting virus, as well as with the nAb titers that increased against early/founder viruses in 22 other participants in the CAPRISA 002 cohort.

They found that titers to the superinfecting virus strains were comparable with those seen in single infections from the rest of the cohort. In contrast, two other superinfecting virus strains developed exceedingly high neutralizing titers against themselves. Also, HIV superinfection did not appear to boost nAb memory responses primed by the initial infection.

Notably, superinfection did not elicit bnAB responses to epitopes conserved in both infecting viruses. The one individual who appeared to have developed a bnAB response, upon analysis, was found to have breadth of response attributable to a single antibody lineage that only affected the superinfecting virus. This indicated that superinfection did not facilitate breadth by directing responses to an Env conserved in both infecting viruses, according to Mr. Sheward and his colleagues.

“HIV superinfection fails to efficiently recruit neutralizing memory B cells and, at best, results in additive nAb responses rather than a synergistic effect leading to cross-neutralization; a distinction that is highly relevant for vaccine design. ... [W]hile sequential immunizations with heterologous Env immunogens may be able to improve the potency of elicited responses, alone, they are unlikely to promote the development of bnAbs,” the researchers concluded.

The study was funded by the Centre for the AIDS Programme of Research in South Africa and the South African Medical Research Council. The authors reported that they had no disclosures.

SOURCE: Sheward DJ et al. Cell Host Microbe. 2018 Oct 10;24[4]:593-9.

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