SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively1,2. These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.
The Omicron subvariant BA.2 accounts for a large majority of the SARS-CoV-2 infection worldwide today1. However, its recent descendants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively2,3. That these novel Omicron subvariants carry additional mutations in their spike proteins raises concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of our COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. On the other hand, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called Class 2 and Class 3 regions of the receptor-binding domain (RBD)4. The F486V mutation found in BA.4/5 facilitates escape from certain Class 1 and Class 2 antibodies to the RBD but compromises the spike affinity for the cellular receptor ACE2. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab (LY-COV1404) retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.
BackgroundDespite global efforts to control HIV among key populations, new infections among men who have sex with men (MSM) and transgender (TG) individuals are still increasing. The increasing HIV epidemic among MSM/TG in China indicates that more effective services are urgently needed. However, policymakers and program managers must have a clear understanding of MSM/TG sexual health in China to improve service delivery. To meet this need, we undertook a scoping review to summarize HIV epidemiology and responses among MSM and TG individuals in China.MethodsWe searched MEDLINE, EMBASE and the Cochrane Library for recent studies on MSM/TG HIV epidemiology and responses. We also included supplemental articles, grey literature, government reports, policy documents, and best practice guidelines.ResultsOverall, HIV prevalence among Chinese MSM was approximately 8 % in 2015 with a higher prevalence observed in Southwest China. TG are not captured in national HIV, STD, or other sexual health surveillance systems. There is limited data sharing between the public health authorities and community-based organizations (CBOs). Like other low and middle income countries, China is challenged by low rates of HIV testing, linkage, and retention. Several pilot interventions have been shown to be effective to increase HIV testing among MSM and TG individuals, but have not been widely scaled up. Data from two randomized controlled trials suggests that crowdsourcing contests can increase HIV testing, creating demand for services while engaging communities.ConclusionImproving HIV surveillance and expanding HIV interventions for Chinese MSM and TG individuals are essential. Further implementation research is needed to ensure high-quality HIV services for MSM and TG individuals in China.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1904-5) contains supplementary material, which is available to authorized users.
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