Modulating the durability of anti-HIV gp120 antibody responses after vaccination: a comment on Wilson & Karp (2015).

In their opinion piece [1], Wilson and Karp discuss the poor durability of the anti-gp120 humoral response, an important feature that poses a significant difficulty for HIV vaccine development [2]. The authors make the case that short-lived anti-gp120 responses are not seen in all studies of HIV-envelope-based vaccines, suggesting that the problem might be solved via vaccine formulation strategies and existing adjuvants. They argue that two clinical trials by Goepfert et al. [3] and Leroux-Roels et al. [4] already show that vaccines containing gp120 formulated in monophosphoryl lipid A-containing adjuvants raise humoral responses that are considerably more durable than what was observed by Yates et al. [5] in the RV144 trial, which tested a different vaccination regimen. We agree with the use of RV144 as a benchmark for comparing HIV-envelope-based vaccine trials as this was a case where humoral anti-gp120 responses were correlates of risk [6]. Vaccine efficacy was roughly 60% early in the trial but declined to about 30% overall as humoral responses waned over time [7]. However, we disagree with the view that the Goepfert et al. and Leroux-Roels et al. examples cited in the opinion piece demonstrate unusually durable anti-gp120 responses or point towards any particular vaccine formulation that solves the durability problem. Questions emerge when one considers the differences in data collection and reporting between studies. One disparity is that timescales vary among the studies. Goepfert et al. report responses in days; Yates et al., in weeks; Leroux-Roels et al., in months. Another variance is that humoral responses are not quantified or reported in the same way. Goepfert et al. report humoral responses as 50% maximal gp120 ELISA binding titres; Leroux-Roels et al., as gp120 ELISA units ml 21. The Yates et al. RV144 study reports anti-gp120 humoral responses as percentages of vaccinees with antibody titres above baseline (per cent 'responders'). One approach to compensate for such differences is to track all humoral responses as a fraction of the apparent peak response (i.e. what is evident from the reported data) versus a normalized timescale. Figure 1 depicts the application of this approach to data from the three studies cited here. It is visually apparent that the persistence of the peak anti-gp120 response is quite similar for all regimens in the Goepfert et al. and Leroux-Roels et al. studies (red and green lines, respectively) after the respective final boosts. Responses decline rapidly to approximately 10% of peak …