A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine.

Impact of the Second Epidemic Wave of SARS-CoV-2: Increased Exposure of Young People

We aimed to use serological surveillance based on serial cross-sectional sampling of residual sera obtained from clinical laboratories to compare the differences in age and sex profiles of infected persons in the first and second waves of SARS-CoV-2 in Corsica, France. Residual sera were obtained, including samples from individuals of all ages collected for routine screening or clinical management by clinical laboratories. All the sera collected were tested for the presence of anti-SARS-CoV-2 IgG using a kit for semi-quantitative detection of IgG antibodies against the S1 domain of the viral spike protein (ELISA-S). Samples that were borderline and positive in ELISA-S were tested with an in-house virus neutralization test. During the second-wave period, we collected between 6 November, 2020 and 12 February, 2021, 4,505 sera from patients aged 0–101 years (60.4% women). The overall weighted seroprevalence of residual sera collected during the second-wave period [8.04% (7.87–9.61)] was significantly higher than the overall weighted seroprevalence estimated at the end of the first wave between 16 April and 15 June, 2020 [5.46% (4.37–7.00)] (p-value = 0.00025). Ninety-eight (30.1%) of the 326 samples tested in the VNT assay had a positive neutralization antibody titer. Estimated seroprevalence increased significantly for men [odds ratio (OR) OR = 1.80 (1.30–2.54); p-value = 0.00026] and for people under 30 years of age [OR = 2.17 (1.46–3.28); p-value = 0.000032]. This increase was observed in young adults aged 20–29 years among whom antibody frequencies were around four-fold higher than those observed at the end of the first wave. In conclusion, our seroprevalence estimates, including the proportion of the participants who had produced neutralizing antibodies, indicate that in February, 2021 the population of Corsica was still far from being protected against SARS-Cov-2 by “herd immunity.”

Role of Herpes Simplex Virus Infection in the Pathogenesis of Facial Paralysis in Mice

To clarify the role and site of herpes simplex virus (HSV) infection in the pathogenesis of facial paralysis, we examined the viral genome by the polymerase chain reaction and the neutralization antibody titer using microplates in an animal model. Following inoculation with HSV type 1 of the KOS strain into mouse auricles, HSV DNA appeared in the ipsilateral facial nerve on the 3rd day, and in bilateral facial nerves and the brain stem on the 10th day only in animals with facial paralysis. In animals without facial paralysis, no HSV DNA was detected in these tissues. The neutralization antibody titer was elevated between 4 and 20 days in all animals, with or without facial paralysis. Facial paralysis developed only on the inoculated side, even though HSV DNA was also present in the contralateral facial nerve. We conclude that HSV infection in the facial nerve and brain stem is prerequisite for facial paralysis, and suggest that an immunologic reaction following viral infection plays a key role in the pathogenesis.