SARS-CoV-2 Omicron BA.2.87.1 Exhibits Higher Susceptibility to Serum Neutralization Than EG.5.1 and JN.1 (preprint)

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions ({Delta}15-26 and {Delta}136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.

Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster (preprint)

SARS-CoV-2-neutralizing antibodies were substantially expanded one month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remained unknown. Here, we addressed this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from 39 adult participants obtained at ~1 month and ~3 months post an XBB.1.5 MV booster. Our findings indicate that the resultant neutralizing antibody titers were robust and generally maintained at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.

Children with allergic asthma sensitized to house dust mites getting better health during COVID-19 pandemic (preprint)

Background: Since December 2019, 2019 novel corona virus (2019-nCov) disease (COVID-19) has extended to most parts of China with more than 80 thousand cases. From Feb 1 to Mar 31 of 2020, all children were asked to stay indoors in China. Then how it affected allergic asthma (AA) sensitized to house dust mites (HDM) in children was interestingly to clarify. Objective: To investigate the changes of clinical characteristics of children with AA sensitized to HDM during COVID-19 pandemic. Method: The data including asthma symptom scores(SS), visual analog scores (VAS), asthma quality of life questionnaire (AQLQ) and medicine scores (MS) as well as respiratory infections, cares, staying up late and diets, collected from children with AA sensitized to HDM from Feb 1 to Mar 31 of 2019 and 2020 retrospectively, were analyzed. Results: There were 85 children with AA sensitized to HDM included in this research. Compared with SS, VAS, AQLQ and MS of the patients from Feb 1 to Mar 31 of 2019, SS, VAS, AQLQ and MS of the patients improved significantly (p<0.05) during COVID-19 pandemic. No respiratory infections occurred among them and they got better cares, had better diets and stayed up late less during COVID-19 pandemic. Conclusion: During COVID-19 pandemic, children with AA sensitized to HDM got better health for staying indoors, which might be associated with no respiratory infections, better cares, better diets and less staying up late.

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants (preprint)

COVID-19 vaccines have recently been updated with the spike protein of SARS-Co-V-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,764-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public.

Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike (preprint)

Although the COVID-19 pandemic has officially ended, SARS-CoV-2 continues to spread and evolve. Recent infections have been dominated by XBB.1.5 and EG.5.1 subvariants. A new subvariant designated BA.2.86 has just emerged, spreading to 21 countries in 5 continents. This virus contains 34 spike mutations compared to its BA.2 predecessor, thereby raising concerns about its propensity to evade existing antibodies. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was not more resistant to human sera than XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from patients who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. The finding that the longer genetic distance of BA.2.86 did not yield a larger antigenic distance was partially explained by the mAb data. While BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the inner face of RBD that is exposed only when this domain is in the up position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.

Antibody Neutralization of Emerging SARS-CoV-2: EG.5.1 and XBC.1.6 (preprint)

SARS-CoV-2 variants EG.5.1 and XBC.1.6 have recently emerged, attracting increased attention due to their rapid expansion globally and in Australia, respectively. EG.5.1 evolved from Omicron subvariant XBB.1.9, harboring additional Q52H and F456L spike substitutions. The F456L mutation is located within the epitopes of many class-1 monoclonal antibodies (mAbs) directed to the receptor-binding domain (RBD), raising concerns about further antibody evasion. XBC.1.6, a descendant of a Delta-BA.2 recombinant, carries 15 additional spike mutations. The extent to which antibody evasion contributes to the growth advantage of XBC.1.6 in Australia remains to be determined. To assess the antibody evasion properties of the emergent variants, we conducted pseudovirus neutralization assays using sera from individuals who received three doses of COVID-19 mRNA monovalent vaccines plus one dose of a BA.5 bivalent vaccine, as well as from patients with BQ or XBB breakthrough infection. The assays were also performed using a panel of 14 mAbs that retained neutralizing activity against prior XBB subvariants. Our data suggested that EG.5.1 was slightly but significantly more resistant (< 2-fold) to neutralization by BQ and XBB breakthrough sera than XBB.1.16, which is known to be antigenically similar to XBB.1.5. Moreover, the F456L mutation in EG.5.1 conferred heightened resistance to certain RBD class-1 mAbs. In contrast, XBC.1.6 was more sensitive to neutralization by sera and mAbs than the XBB subvariants. Notably, XBB breakthrough sera retained only weak neutralization activity against XBB subvariants. In summary, EG.5.1 and XBC.1.6 exhibited distinct antibody evasion properties. The recent global expansion of EG.5.1 might be attributable, in part, to its enhanced neutralization resistance. That XBB breakthrough infections did not elicit a robust antibody neutralization response against XBB subvariants is indicative of immunological imprinting. The high prevalence of XBC.1.6 in Australia is not due to enhanced antibody evasion.

SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster (preprint)

Bivalent COVID-19 mRNA vaccines expressing both the ancestral D614G and Omicron BA.5 spike proteins were introduced in August 2022 with the goal of broadening immunity to emerging SARS-CoV-2 Omicron subvariants. Subsequent studies on bivalent boosters found neutralizing antibody responses similar to boosters with the original monovalent vaccine, likely the result of immunological imprinting. Guidelines allow for administration of a second bivalent booster in high-risk groups, but it remains unknown whether this would broaden antibody responses. To address this question, we assessed longitudinal serum SARS-CoV-2-neutralizing titers in 18 elderly immunocompetent individuals (mean age 69) following a fourth monovalent booster and two BA.5 bivalent booster vaccines using pseudovirus neutralization assays against D614G, Omicron BA.5, and Omicron XBB.1.5. There was a small but significant increase in peak neutralizing antibody responses against Omicron BA.5 and XBB.1.5 following the first bivalent booster, but no significant increase in peak titers following the second bivalent booster. Omicron-specific neutralizing titers remained low after both doses of the BA.5 bivalent booster. Our results suggest that a second dose of the BA.5 bivalent booster is not sufficient to broaden antibody responses and to overcome immunological imprinting. A monovalent vaccine targeting only the spike of the recently dominant SARS-CoV-2 may mitigate the back boosting associated with the original antigenic sin.

The Effect of Health Action Process Approach on Adherence to Infection Prevention and Control Measures Among Chinese Healthcare Workers in the Post-pandemic Period of COVID-19 (preprint)

Background: Although the COVID-19 pandemic has been brought under control, strict infection and control measures are still recommended for healthcare workers to prevent the rebound of the pandemic. However, adherence to prevention measures might be decreased due to fatigue caused by the prolonged duration of the pandemic.  Objective: This study examines the effects of social-cognitive factors suggested in the health action process approach on adherence to infection prevention and control measures among Chinese healthcare workers two years after the onset of the COVID-19 pandemic. Methods: A total of 521 healthcare workers from two COVID-19 designated hospitals in Beijing participated in the survey in August 2021 and reported risk perception, outcome expectance, action self-efficacy, preventive intention, action control, and prevention behaviors during work. Results: 1) Action self-efficacy and outcome expectancy were positively associated with intention to adhere to preventive measures. 2) Action control mediated the association between intention and preventive behaviors during work. Conclusion: Social-cognitive factors such as action self-efficacy, action control, and intention should be addressed to improve healthcare workers’ adherence to infection and control measures during the COVID-19 pandemic.

Deep immunological imprinting due to the ancestral spike in the current bivalent COVID-19 vaccine (preprint)

With the aim of broadening immune responses against the evolving SARS-CoV-2 Omicron variants, bivalent COVID-19 mRNA vaccines that encode the ancestral and Omicron BA.5 spike proteins have been authorized for clinical use, supplanting the original monovalent counterpart in numerous countries. However, recent studies have demonstrated that administering either a monovalent or bivalent vaccine as a fourth vaccine dose results in similar neutralizing antibody titers against the latest Omicron subvariants, raising the possibility of immunological imprinting. Utilizing binding immunoassays, pseudotyped virus neutralization assays, and antigenic mapping, we investigated antibody responses from 72 participants who received three monovalent mRNA vaccine doses followed by either a bivalent or monovalent booster, or who experienced breakthrough infections with the BA.5 or BQ subvariant after vaccinations with an original monovalent vaccine. Compared to a monovalent booster, the bivalent booster did not yield noticeably higher binding titers to D614G, BA.5, and BQ.1.1 spike proteins, nor higher virus-neutralizing titers against SARS-CoV-2 variants including the predominant XBB.1.5 and the emergent XBB.1.16. However, sera from breakthrough infection cohorts neutralized Omicron subvariants significantly better. Multiple analyses of these results, including antigenic mapping, made clear that inclusion of the ancestral spike prevents the broadening of antibodies to the BA.5 component in the bivalent vaccine, thereby defeating its intended goal. Our findings suggest that the ancestral spike in the current bivalent COVID-19 vaccine is the cause of deep immunological imprinting. Its removal from future vaccine compositions is therefore strongly recommended.

Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking (preprint)

SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.

Willingness to practice medicine and related influential factors among Medical Undergraduates during COVID-19: a cross-sectional study (preprint)

Background Medical undergraduates are the future workforce, and their job preferences can directly impact the quality of healthcare services in China, especially during the coronavirus (COVID-19) pandemic. We aim to understand the status of the willingness to practice medicine among medical undergraduates and to analyze the related influential factors.Methods During the COVID-19 epidemic, we conducted a cross-sectional survey from 15 February 2022 to 31 May 2022 through an online platform to collect information about characteristics, psychology, and motivations for the career choice. The general self-efficacy scale (GSES) was used to assess medical students’ self-efficacy perceptions. Multivariate logistic regression was used to analyse influencing factors of willingness to practice medicine.Results A total of 2348 valid questionnaires were included, and 1573 (66.99%) were willing to practice medicine for medical undergraduates after graduation. The mean GESE scores in the willingness group (2.87 ± 0.54) were significantly higher than those in the unwillingness group (2.73 ± 0.49). The multiple logistic regression showed that several factors were positively associated with willingness to practice medicine as a career, including students’ GSES score (OR = 1.72), personal ideals (OR = 2.04), family support (OR = 1.48), high income (OR = 1.81), and social respect (OR = 2.14). Compared with those very afraid of COVID-19, students who were not afraid at all had a higher preference for choosing the medical profession as a career. In addition, students thinking of high tension in the doctor-patient relationship, heavy workload, and long training were less likely to choose medical work after graduation.Conclusions There was a relatively high level of willingness to practice medicine among medical undergraduates after graduation. Psychological factors, personal preferences, career needs or preferences, and the impact of the COVID-19 pandemic are associated with this willingness.

Impaired potency of neutralizing antibodies against cell-cell fusion mediated by SARS-CoV-2 (preprint)

The SARS-CoV-2 Omicron subvariants have dominated the pandemic due to their high transmissibility and immune evasion conferred by the spike mutations. The Omicron subvariants can spread by cell-free virus infection and cell-cell fusion, the latter of which is more effective but has not been extensively investigated. In this study, we developed a simple and high-throughput assay that provides a rapid readout to quantify cell-cell fusion mediated by the SARS-CoV-2 spike proteins without using live or pseudotyped virus. This assay can be used to identify variants of concern and to screen for prophylactic and therapeutic agents. We further evaluated a panel of monoclonal antibodies (mAbs) and vaccinee sera against D614G and Omicron subvariants, finding that cell-cell fusion is substantially more resistant to mAb and serum inhibition than cell-free virus infection. Such results have important implications for the development of vaccines and antiviral antibody drugs against cell-cell fusion induced by SARS-CoV-2 spikes.

SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster (preprint)

Bivalent mRNA vaccine boosters expressing Omicron BA.5 spike and ancestral D614G spike were introduced to attempt to boost waning antibody titers and broaden coverage against emerging SARS-CoV-2 lineages. Previous reports showed that peak serum neutralizing antibody (NAb) titers against SARS-CoV-2 variants following bivalent booster were similar to peak titers following monovalent booster. It remains unknown whether these antibody responses would diverge over time. We assessed serum virus-neutralizing titers in 41 participants who received three monovalent mRNA vaccine doses followed by bivalent booster, monovalent booster, or BA.5 breakthrough infection at one month and three months after the last vaccine dose or breakthrough infection using pseudovirus neutralization assays against D614G and Omicron subvariants (BA.2, BA.5, BQ.1.1, and XBB.1.5). There was no significant difference at one month and three months post-booster for the two booster cohorts. BA.5 breakthrough patients exhibited significantly higher NAb titers at three months against all Omicron subvariants tested compared against monovalent and bivalent booster cohorts. There was a 2-fold drop in mean NAb titers in the booster cohorts between one and three month time points, but no discernible waning of titers in the BA.5 breakthrough cohort over the same period. Our results suggest that NAb titers after boosting with one dose of bivalent mRNA vaccine are not higher than boosting with monovalent vaccine. Perhaps inclusion of D614G spike in the bivalent booster exacerbates the challenge posed by immunological imprinting. Hope remains that a second bivalent booster could induce superior NAb responses against emerging variants.

Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 (preprint)

The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5' end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2'-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host's innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants and characterized using X-ray crystallography, biophysical assays, and enhanced sampling simulations. In contrast to other proteins such as spike and NSP6, NSP10 is significantly less prone to mutation due to its crucial role in replication. The functional effects of the variants were examined for their impact on the binding affinity and stability of both NSP14-NSP10 and NSP16-NSP10 complexes. These results highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. These results also indicate that there is limited capacity for the virus to overcome inhibitors targeting NSP10 via the generation of variants in inhibitor binding pockets.

Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants (preprint)

The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.

Trends of myopia development among primary and junior school students in the post-COVID-19 epidemic period

Purpose To investigate the trends of myopia among primary and junior school students in the post-COVID-19 epidemic period. Method A prospective of cross-sectional study using spot photoscreenings in 123,538 children among primary and junior school students from 2019 to 2021 was conducted to evaluate the development of myopia in Xuzhou, China in the post-COVID-19 epidemic period. Equivalent refraction and the prevalence of myopia were recorded. Results The spherical equivalent refraction of myopia decreased across all grades except grade 1 (0.23 ± 0.56 D in 2019, 0.24 ± 0.63 D in 2020) from 2019 to 2020. However, refraction exhibited a hyperopic shift in 2021 compared to 2020 for grades 1–5 (no significant decreased for grade 4). The prevalence of myopia in all grades increased in 2020 compared to 2019, and the most dramatic changes were observed from grades 2–5 and grades 7–8 (P < 0.05). The changes in myopia prevalence in grades 1–4 were mild, and the reduction in myopia for Grade 5 is significant from 2020 to 2021. Nevertheless, students in grades 6 and 9 exhibited the greatest growth in myopia prevalence (P < 0.01). All grades had higher myopia prevalence in 2021 compared with 2019, except grade 1 (P = 0.25). The prevalence of myopia in girls was higher compared with boys, and the urban myopia prevalence was higher than in rural areas over the 3 years except in 2019 (P = 0.18). Conclusions The prevalence of myopia increased during the COVID-19 epidemic. However, the spherical equivalent refraction of lower grade children drifted to hyperopia and the trends of myopia development remained stable in the post-COVID-19 epidemic period. We should be more concerned about the prevalence of myopia in graduating for the primary or junior grades in the future.

A web-based survey of SARS-CoV-2 vaccination and its adverse effects in Chinese postoperative patients with breast cancer: a cross-sectional study

Background Vaccination against SARS-CoV-2 has been the most important strategy for preventing infection and controlling pandemics of coronavirus disease 2019 (COVID-19). Cancer patients have a significantly higher risk of infection with COVID-19 because of their impaired immunity. Breast cancer is the most common female malignant tumor in the world. However, studies on COVID-19 vaccination in breast cancer patients are scarce, so that more information is needed to guide vaccination in these. Methods We conducted a web-based questionnaire survey on SARS-CoV-2 vaccination in breast cancer patient. Questionnaires completed by non-postoperative patients will be considered invalid. The main variables in the questionnaire including vaccination status, willingness to get the vaccines, candidate factors, and measures of adverse events in vaccinated individuals were used for analysis. Univariate and multivariate logistic regression was used to estimate the associations. Results Among 947 valid online questionnaires, 341 (36.0%) accepted SARS-CoV-2 vaccination, while 606 (64.0%) did not. There were significant differences in age, current treatment, time since surgery, and symptoms of anxiety and depression between the two groups. Compared to vaccinated patients, we identified current treatment [odds ratio (OR) =0.51 for endocrine therapy;95% confidence interval (CI): 0.29–0.89], time since surgery (OR =22.49 for 1–2 years;95% CI: 12.31–41.10;OR =8.49 for 2–5 years;95% CI: 4.98–14.46;OR =1.79 for >5 years;95% CI: 1.11–2.89), and symptoms of depression (OR =2.48;95% CI: 1.19–5.15) as significant factors for being unvaccinated. The overall incidence of adverse reactions was 43.1%, and the most common local and systemic adverse reactions were pain (28.4%) and fatigue (8.8%). However, about 76.6% of the unvaccinated participants were willing to be vaccinated. Conclusions Compared to the general population, postoperative patients with breast cancer had a lower rate of vaccination for SARS-CoV-2. Receiving treatment, a shorter time since surgery, and symptoms of depression were associated with being unvaccinated. However, about 76.6% of the unvaccinated participants were willing to be vaccinated. Although our study showed that there were adverse effects of SARS-CoV-2 vaccines, such as pain, fatigue, they are common adverse effects of routine vaccination. We believe that vaccination against COVID-19 is safe in postoperative patients with breast cancer.

Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot (preprint)

The SARS-CoV-2 Omicron variant and its numerous sub-lineages have exhibited a striking ability to evade humoral immune responses induced by prior vaccination or infection. The Food and Drug Administration (FDA) has recently granted Emergency Use Authorizations (EUAs) to new bivalent formulations of the original Moderna and Pfizer mRNA SARS-CoV-2 vaccines that target both the ancestral strain as well as the Omicron BA.4/BA.5 variant. Despite their widespread use as a vaccine boost, little is known about the antibody responses induced in humans. Here, we collected sera from several clinical cohorts: individuals after three or four doses of the original monovalent mRNA vaccines, individuals receiving the new bivalent vaccines as a fourth dose, and individuals with BA.4/BA.5 breakthrough infection following mRNA vaccination. Using pseudovirus neutralization assays, these sera were tested for neutralization against an ancestral SARS-CoV-2 strain, several Omicron sub-lineages, and several related sarbecoviruses. At ~3-5 weeks post booster shot, individuals who received a fourth vaccine dose with a bivalent mRNA vaccine targeting BA.4/BA.5 had similar neutralizing antibody titers as those receiving a fourth monovalent mRNA vaccine against all SARS-CoV-2 variants tested, including BA.4/BA.5. Those who received a fourth monovalent vaccine dose had a slightly higher neutralizing antibody titers than those who received the bivalent vaccine against three related sarbecoviruses: SARS-CoV, GD-Pangolin, and WIV1. When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation.

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes. (preprint)

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed and open. The locked conformations feature tightly packed trimers with structural elements incompatible with RBD in "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably due to their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. Intriguingly, locked conformations were the only conformations captured for S proteins of bat and pangolin origin SARS-related coronaviruses. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures to other available spike structures of Sarbecoviruses to identify conserved features and discuss their possible functions.