Abstract
Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen. Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient. In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor. Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database). Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database. A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies. The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites. Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies. For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
Highlights
HIV-1 was identified as the pathogen of acquired immunodeficiency syndrome (AIDS) three decades ago (Gottlieb and Schroff, 1981; Barre-Sinoussi et al, 1983; Gallo et al, 1983; Dalgleish et al, 1984); the development of efficient and safe vaccines is still under way (Moore, 2018; Burton, 2019)
BNabs isolated in the natural HIV-1 infection provide a prototype that could be elicited by vaccines (Van Gils and Sanders, 2013; Bonsignori et al, 2017; Haynes and Mascola, 2017)
Our results showed that all of the Env pseudoviruses from DRVI01 were resistant to five antibody DRVIA7 (A7) reconstituted antibodies (Table 3), which indicated that functional Env clones binding to the A7 lineage may be relatively rare
Summary
HIV-1 was identified as the pathogen of acquired immunodeficiency syndrome (AIDS) three decades ago (Gottlieb and Schroff, 1981; Barre-Sinoussi et al, 1983; Gallo et al, 1983; Dalgleish et al, 1984); the development of efficient and safe vaccines is still under way (Moore, 2018; Burton, 2019). Neutralization antibodies (bNAbs) targeting Env can protect animal models from the challenge of SHIV-1, neutralize most global circulating strains, and accelerate elimination of HIV-1-infected cells (Lu et al, 2016; Julg et al, 2017), eliciting bNAbs is an important goal of HIV-1 vaccines. With the wide utilization of new technologies such as single cell antibody cloning techniques, micro-neutralization assay, and B cell repertoire analysis (Simek et al, 2009; Walker et al, 2009, 2011; Huang et al, 2013; Zhu et al, 2013), hundreds of bNAbs were successively isolated from HIV-1-infected individuals (Burton and Hangartner, 2016; Wu and Kong, 2016). Further exploring the general characteristics underlying the development of bNAbs would provide insights into efficient vaccines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
