Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma

Abstract

Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2 pseudoviruses. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.

Monoclonal antibody therapies against SARS-CoV-2

“…Broadly neutralising antibodies targeting cross-reactive epitopes found in all or most variants are sought after when designing therapies for antigenically variable viruses, such as HIV-1 and SARS-CoV-2. 140 Within the genus Betacoronavirus, broadly neutralising antibodies have neutralising activity across all sarbecoviruses ( appendix p 7 ). 141 Pan-sarbecovirus antibodies are elicited by BNT162b2 vaccination in SARS-CoV survivors.…”

Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

“…Plasmodium and human immunodeficiency virus (HIV), both microorganisms being endemic in Africa, have been shown to induce in patients nNAbs that can cross-react with SARS-CoV-2, but these antibodies do not correlate with more severe forms of COVID-19 disease [44] , [45] , [46] . Polyclonal plasma from HIV-infected children cross-reacts with SARS-CoV-2 but, to our knowledge, there are no data in the literature on their possible involvement in ADE [47] . Moreover, cross-reactivity of SARS-CoV-2 antigen/antibodies can lead to HIV-antibody false positive results in chemiluminescent HIV immunoassays [48] .…”

Use of oral polio vaccine and the incidence of COVID-19 in the world

“…On the other hand, while the attenuated poliovirus in the OPV can contaminate the close contacts of the vaccinated child (particularly where the hygienic standards are low) and thereby protect them from other infections [ 17 ], MMR and BCG can only affect the vaccinated person. Furthermore, recent experimental evidence suggests that antibodies generated in response to other viral pathogens may cross react with SARS-COV-2 and provide heterologous protection [ 28 ]. Controlling these covariates is complicated mainly because of the nature of our study—the inherent inability to make individual level causal inferences based on the aggregate data used in an ecological study.…”