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Consistent elicitation of cross-clade HIV-neutralizing responses achieved in guinea pigs after fusion peptide priming by repetitive envelope trimer boosting.
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- المؤلفون: Cheng, Cheng1; Xu, Kai1; Kong, Rui1; Chuang, Gwo-Yu1; Corrigan, Angela R.1; Geng, Hui1; Hill, Kurt R.1; Jafari, Alexander J.1; O’Dell, Sijy1; Ou, Li1; Rawi, Reda1; Rowshan, Ariana P.1; Sarfo, Edward K.1; Sastry, Mallika1; Saunders, Kevin O.2; Schmidt, Stephen D.1; Wang, Shuishu1; Wu, Winston1; Zhang, Baoshan1; Doria-Rose, Nicole A.1
- المصدر:
PLoS ONE. 4/17/2019, Vol. 14 Issue 4, p1-20. 20p.
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
The vaccine elicitation of broadly neutralizing responses is a central goal of HIV research. Recently, we elicited cross-clade neutralizing responses against the N terminus of the fusion peptide (FP), a critical component of the HIV-entry machinery. While the consistency of the elicited cross-clade neutralizing responses was good in mice, it was poor in guinea pigs: after seven immunizations comprising either envelope (Env) trimer or FP coupled to a carrier, serum from only one of five animals could neutralize a majority of a cross-clade panel of 19 wild-type strains. Such a low response rate—only 20%—made increasing consistency an imperative. Here, we show that additional Env-trimer immunizations could boost broad FP-directed neutralizing responses in a majority of immunized animals. The first boost involved a heterologous Env trimer developed from the transmitted founder clade C strain of donor CH505, and the second boost involved a cocktail that combined the CH505 trimer with a trimer from the BG505 strain. After boosting, sera from three of five animals neutralized a majority of the 19-strain panel and serum from a fourth animal neutralized 8 strains. We demonstrate that cross-reactive serum neutralization targeted the FP by blocking neutralization with soluble fusion peptide. The FP competition revealed two categories of elicited responses: an autologous response to the BG505 strain of high potency (~10,000 ID50), which was not competed by soluble FP, and a heterologous response of lower potency, which was competed by soluble FP. While the autologous response could increase rapidly in response to Env-trimer boost, the heterologous neutralizing response increased more slowly. Overall, repetitive Env-trimer immunizations appeared to boost low titer FP-carrier primed responses to detectable levels, yielding cross-clade neutralization. The consistent trimer-boosted neutralizing responses described here add to accumulating evidence for the vaccine utility of the FP site of HIV vulnerability. [ABSTRACT FROM AUTHOR]
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