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The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa 1-3 . It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development 4 , and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India 1-5 . Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries 6 . The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2-also termed the Delta variant-is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

This corrects the article DOI: 10.1038/nature21710.

The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells. Notably, productive HIV-1 infection of T-cell-receptor-stimulated CD4 T cells is not associated with CD32a expression, suggesting that a quiescence-dependent mechanism is required for its induction. Using blood samples from HIV-1-positive participants receiving suppressive antiretroviral therapy, we identify a subpopulation of 0.012% of CD4 T cells that express CD32a and host up to three copies of HIV DNA per cell. This CD32a + reservoir was highly enriched in inducible replication-competent proviruses and can be predominant in some participants. Our discovery that CD32a + lymphocytes represent the elusive HIV-1 reservoir may lead to insights that will facilitate the specific targeting and elimination of this reservoir.

The CD4 and the cryptic coreceptor binding sites of the HIV-1 envelope glycoprotein are key to viral attachment and entry. We developed new molecules comprising a CD4 mimetic peptide linked to anionic compounds (mCD4.1-HS 12 and mCD4.1-PS1), that block the CD4-gp120 interaction and simultaneously induce the exposure of the cryptic coreceptor binding site, rendering it accessible to HS 12 - or PS1- mediated inhibition. Using a cynomolgus macaque model of vaginal challenge with SHIV162P3, we report that mCD4.1-PS1, formulated into a hydroxyethyl-cellulose gel provides 83% protection (5/6 animals). We next engineered the mCD4 moiety of the compound, giving rise to mCD4.2 and mCD4.3 that, when conjugated to PS1, inhibited cell-free and cell-associated HIV-1 with particularly low IC 50 , in the nM to pM range, including some viral strains that were resistant to the parent molecule mCD4.1. These chemically defined molecules, which target major sites of vulnerability of gp120, are stable for at least 48 hours in conditions replicating the vaginal milieu (37 °C, pH 4.5). They efficiently mimic several large gp120 ligands, including CD4, coreceptor or neutralizing antibodies, to which their efficacy compares very favorably, despite a molecular mass reduced to 5500 Da. Together, these results support the development of such molecules as potential microbicides.