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.
Highlights
Highly active antiretroviral therapy suppresses HIV-1 replication effectively[1], it does not fully eradicate the virus, produces undesirable side effects, requires life-long treatment to maintain suppression[2], and is not accessible to all who need it
We found higher GMTs for former plasma donor (FPD) cohort than that of intravenous drug users (IDUs) cohort against inter-subtype viruses (Fig. 3b), suggesting more robust cross-reactive neutralizing antibody (NAb) response over time as well
We compared NAb profiles between the IDU and FPD cohorts. Data from both cohorts showed that more than 50% of plasma samples could neutralize at least 50% of virus strains tested, indicating that the human immune system is capable of mounting moderate neutralizing antibody responses in general, as has been observed previously in another large cohort study[31]
Summary
Highly active antiretroviral therapy suppresses HIV-1 replication effectively[1], it does not fully eradicate the virus, produces undesirable side effects, requires life-long treatment to maintain suppression[2], and is not accessible to all who need it. We assessed the prevalence, breadth, and potency of NAb responses in CRF07_BC chronically infected individuals (infection time of 3–5 years) using a large multi-subtype panel of 30 tier 2–3 HIV-1 Env-pseudotyped virus strains which covered the main subtypes circulating in China and East Asia. We comprehensively compared the neutralization pattern of this cohort with that of subtype B’ chronically infected individuals from the FPD cohort in China, infected for more than ten years, as described previously[15,27] This comparison study in NAb patterns between the two cohorts offers a unique opportunity to observe and profile how broad NAbs evolve over time at the population level and in a single elite neutralizer, which could guide regional NAb-based prophylactic and therapeutic strategies development
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