1. Mucosal AIDS virus transmission is enhanced by antiviral IgG isolated early in infection
- Author
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Bishal Marasini, Akil Akhtar, Samir K. Lakhashe, Dinesh Hariraju, Ruth M. Ruprecht, Sarah J. Ratcliffe, and Hemant K. Vyas
- Subjects
viruses ,Immunology ,Simian Acquired Immunodeficiency Syndrome ,HIV Infections ,Viremia ,HIV Antibodies ,complement-mediated antibody-dependent enhancement ,Antiviral Agents ,Macaque ,Neutralization ,Virus ,rhesus macaques ,Chimera (genetics) ,Basic Science ,biology.animal ,medicine ,Animals ,Immunology and Allergy ,enhancing antibodies ,AIDS Vaccines ,biology ,business.industry ,HIV ,medicine.disease ,Virology ,Infectious Diseases ,SHIV ,Viral replication ,Immunization ,Immunoglobulin G ,HIV-1 ,biology.protein ,Simian Immunodeficiency Virus ,Antibody ,business ,ADE - Abstract
Objective Antibody-dependent enhancement (ADE) affects host-virus dynamics in fundamentally different ways: i) enhancement of initial virus acquisition, and/or ii) increased disease progression/severity. Here we address the question whether anti-HIV-1 antibodies can enhance initial infection. While cell-culture experiments hinted at this possibility, in-vivo proof remained elusive. Design We used passive immunization in nonhuman primates challenged with simian-human immunodeficiency virus (SHIV), a chimera expressing HIV-1 envelope. We purified IgG from rhesus monkeys with early-stage SHIV infection - before cross-neutralizing anti-HIV-1 antibodies had developed - and screened for maximal complement-mediated antibody-dependent enhancement (C'-ADE) of viral replication with a SHIV strain phylogenetically distinct from that harbored by IgG donor macaques. IgG fractions with maximal C'-ADE but lacking neutralization were combined to yield enhancing anti-SHIV IgG (enSHIVIG). Results We serially enrolled naive macaques (Group 1) to determine the minimal and 50% animal infectious doses required to establish persistent infection after intrarectal SHIV challenge. The first animal was inoculated with a 1:10 virus-stock dilution; after this animal's viral RNA load was >104copies/ml, the next macaque was challenged with 10x less virus, a process repeated until viremia no longer ensued. Group 2 was pretreated intravenously with enSHIVIG 24 hours before SHIV challenge. Overall, Group 2 macaques required 3.4-fold less virus compared to controls (p = 0.002). This finding is consistent with enhanced susceptibility of the passively immunized animals to mucosal SHIV challenge. Conclusion These passive immunization data give proof of IgG-mediated enhanced virus acquisition after mucosal exposure - a potential concern for antibody-based AIDS vaccine development.
- Published
- 2021