Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy

Abstract

Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B’-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B’-infected individuals with longer infection length. However, subtype B’-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.

Identification of a novel broadly HIV-1-neutralizing antibody from a CRF01_AE-infected Chinese donor

“…A total of 29% of plasma samples neutralized more than 80% of the tested viral strains, and 64% neutralized more than 50% in Chinese individuals infected with HIV-1 clade B 28 . The proportions of neutralizing breadths >80 and 50% were 18 and 53% in CRF07_BC-infected Chinese individuals, respectively 29 . Our group and colleagues identified a monoclonal nAb (DRVIA7) with modest neutralizing breadth from a HIV-1 B-infected Chinese donor, which was the first VRC01-like antibody isolated from Chinese donors and provided an opportunity to investigate the crucial events in the early stages of VRC01-like antibody development.…”

“…A Global Panel of reference Env clones was established by the Montefiori group at Duke University, which facilitated highly standardized assessments of neutralizing antibodies across multiple HIV-1 research platforms in different parts of the world 54 . Another separate panel containing 25 viruses was compiled by the Shao group at the Division of Research on Virology and Immunology (DRVI Panel) of China CDC, which reflected the HIV-1 epidemic in China and has been utilized in previous studies to evaluate neutralizing antibody responses 16 , 28 , 29 . Pseudoviruses HIV-1 BG505_T332N , HIV-1 BJMSM2316_N160K , and HIV-1 BJMSM2316_N332A were generated by site-directed mutagenesis based on HIV-1 BG505 and HIV-1 BJMSM2316 in this study.…”

Multi-Envelope HIV-1 Vaccine Development: Two Targeted Immune Pathways, One Desired Protective Outcome

“…During the course of chronic infection, most people living with HIV-1 are eventually capable of making a polyclonal antibody response with at least moderate, but significant, breadth of coverage. Hraber et al reported that *50% of samples from chronically HIV-1-infected individuals neutralized at least 50% of 219 envelope-pseudotyped viruses, and Hu et al reported that 53% of samples from chronically HIV-1-infected individuals neutralized more than 50% of 30 envelope-pseudotyped viruses (41,43). Although immune responses in chronically infected patients cannot clear HIV-1 infections, the induction of similar responses by vaccination before an HIV-1 exposure is expected to be protective.…”

Long-term and low-level envelope C2V3 stimulation from highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1 infected individuals

“…The HIV-1 Env glycoprotein is highly immunogenic but, in general, the antibodies elicited by it during infection lack neutralizing breadth or potency against primary HIV-1 strains thus failing to inhibit viral replication in infected individuals 1,2 . In natural infection only 5% to 30% of adults develop broadly neutralizing antibodies (bNAbs) after several years of infection 2,3,4,5,6,7 and these bNAbs have little impact in the control of the infection due to the continuous capacity of HIV-1 to diversify and escape these antibodies 5,8,9 . However, some recombinant human bNAbs supress viral replication in HIV-1 infected individuals 10,11,12,13,14,15 , prevent human infection by some HIV-1 strains 16 , and passive immunization in animal models can protect from infection and/or disease progression (reviewed in 17 ).…”