Neutralising capacity against Delta (B.1.617.2) and other variants of concern following Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in health care workers,Israel

SARS-CoV-2 Delta (B.1.617.2) variant of concern (VOC) and other VOCs are spreading in Europe. Micro-neutralisation assays with sera obtained after Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in 36 healthcare workers (31 female) demonstrated significant fold change reduction in neutralising titres compared with the original virus: Gamma (P.1) 2.3, Beta (B.1.351) 10.4, Delta 2.1 and 2.6. The reduction of the Alpha (B.1.1.7) variant was not significant. Despite being lower, remaining neutralisation capacity conferred by Comirnaty against Delta and other VOCs is probably protective.     

Protective Immunity against Gamma and Zeta Variants after Inactivated SARS-CoV-2 Virus Immunization

The persistent circulation of SARS-CoV-2 represents an ongoing global threat due to the emergence of new viral variants that can sometimes evade the immune system of previously exposed or vaccinated individuals. We conducted a follow-up study of adult individuals that had received an inactivated SARS-CoV-2 vaccine, evaluating antibody production and neutralizing activity over a period of 6 months. In addition, we performed mice immunization with inactivated SARS-CoV-2, and evaluated the immune response and pathological outcomes against Gamma and Zeta variant infection. Vaccinated individuals produced high levels of antibodies with robust neutralizing activity, which was significantly reduced against Gamma and Zeta variants. Production of IgG anti-S antibodies and neutralizing activity robustly reduced after 6 months of vaccination. Immunized mice demonstrated cellular response against Gamma and Zeta variants, and after viral infection, reduced viral loads, IL-6 expression, and histopathological outcome in the lungs. TNF levels were unchanged in immunized or not immunized mice after infection with the Gamma variant. Furthermore, serum neutralization activity rapidly increases after infection with the Gamma and Zeta variants. Our data suggest that immunization with inactivated WT SARS-CoV-2 induces a promptly responsive cross-reactive immunity response against the Gamma and Zeta variants, reducing COVID-19 pathological outcomes.     

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.     

Neutralization of SARS-CoV-2 Variants by Serum from BNT162b2 Vaccine Recipients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved rapidly, leading to viral lineages characterized by multiple mutations in the spike protein, which could potentially confer to the virus the ability to avoid the vaccine-induced immune response, making the vaccines less effective or ineffective. Here, we initially evaluated the neutralization capabilities in vitro by serum neutralization (SN) of six serum samples collected from recipients of the BNT162b2 vaccine against 11 SARS-CoV-2 isolates belonging to the major SARS-CoV-2 lineages that had been circulating in Italy. Then, we considered 30 additional serum samples by SN assay against the dominant B.1.617.2 (Delta) variant. A B.1 lineage isolate was used as a reference. In the first analysis, significant differences when compared with the reference strain (p > 0.05) were not evidenced; instead, when the panel of 30 sera was tested against the B.1.617.2 (Delta) variant, a significant (p = 0.0015) 2.38-fold reduction in neutralizing titres compared with the reference after the first vaccine dose was demonstrated. After the second vaccine dose, the reduction was not significant (p = 0.1835). This study highlights that the BNT162b2 vaccine stimulates a humoral response able to neutralize all tested SARS-CoV-2 variants, thus suggesting a prominent role in mitigating the impact of the SARS-CoV-2 pandemic in real-world conditions. Long-term follow-up is currently ongoing.     

CoronaVac and ChAdOx1 Vaccination and Gamma Infection Elicited Neutralizing Antibodies against the SARS-CoV-2 Delta Variant

The emergence of new SARS-CoV-2 variants represents a constant threat to world public health. The SARS-CoV-2 Delta variant was identified in late 2020 in India; since then, it has spread to many other countries, replacing other predominant lineages and raising concerns about vaccination efficiency. We evaluated the sensitivity of the Delta variant to antibodies elicited by COVID-19 vaccinated (CoronaVac and ChAdOx1) and convalescent individuals previously infected by earlier lineages and by the Gamma variant. No reduction in the neutralizing efficacy of the Delta variant was observed when compared to B lineage and a reduced neutralization was observed for the Gamma variant. Our results indicate that neutralization of the Delta variant is not compromised in individuals vaccinated by CoronaVac or ChAdOx1; however, a reduction in neutralization efficacy is expected for individuals infected by the Gamma variant, highlighting the importance of continuous vaccination even for previously infected individuals.     

Characterization of a Broadly Neutralizing Monoclonal Antibody against SARS-CoV-2 Variants

The constant mutation of SARS-CoV-2 has led to the emergence of new variants, which call for urgent effective therapeutic interventions. The trimeric spike (S) protein of SARS-CoV-2 is highly immunogenic with the receptor-binding domain (RBD) that binds first to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and is therefore the target of many neutralizing antibodies. In this study, we characterized a broadly neutralizing monoclonal antibody (mAb) 9G8, which shows potent neutralization against the authentic SARS-CoV-2 wild-type (WT), Alpha (B.1.1.7), and Delta (1.617.2) viruses. Furthermore, mAb 9G8 also displayed a prominent neutralizing efficacy in the SARS-CoV-2 surrogate virus neutralization test (sVNT) against the Epsilon (B.1.429/7), Kappa (B.1.617.1), Gamma (P.1), Beta (B.1.351), and Delta Plus (1.617.2.1) RBD variants in addition to the variants mentioned above. Based on our in vitro escape mutant studies, we proved that the mutations V483F and Y489H within the RBD were involved in ACE2 binding and caused the neutralizing evasion of the virus from mAb 9G8. The development of such a cross-reactive neutralizing antibody against majority of the SARS-CoV-2 variants provides an important insight into pursuing future therapeutic agents for the prevention and treatment of COVID-19.     

The impact of spike mutated variants of SARS-CoV2 [Alpha,Beta, Gamma,Delta, and Lambda] on the efficacy of subunit recombinant vaccines

Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use in humans. Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. However, the major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the variants of SARS-CoV-2 like B.1.1.7 (Alpha), B.1.351 (Beta) and P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda). The Spike protein (S) is a potential fragment for use as an antigen in vaccine development. This protein plays a crucial role in the first step of the infection process, as it binds to Angiotensin-Converting Enzyme 2 (ACE2) receptor and enters the host cell after binding. Immunization-induced specific antibodies against the receptor binding domain (RBD) may block and effectively prevent virus invasion. The focus of this review is the impact of spike mutated variants of SARS-CoV2 (Alpha, Beta, Gamma, Delta, and Lambda) on the efficacy of subunit recombinant vaccines. To date, a low or no significant impact on vaccine efficacy against Alpha and Delta variants has been reported. Such an impact on vaccine efficacy for Beta, Delta, Gamma, and Lambda variants may be even greater compared to the Alpha variant. Nonetheless, more comprehensive analyses are needed to assess the real impact on vaccine efficacy brought about by SARS-CoV-2 variants.     

The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.     

The Divergent Pattern of SARS-CoV-2 Variant Predominance and Transmission Dynamics in the Brazilian Island of Ilhabela

Our effort in SARS-CoV-2 genomic surveillance in Brazil has detected the Alpha Variant of Concern with a predominance higher than 75% in the population of Ilhabela island (São Paulo State) at a time when the Gamma VOC was already predominating the mainland raised concerns for closer surveillance on this island. Therefore, we intensified the surveillance for 24 weeks by generating data from 34% of local positive cases. Our data show that the patterns of VOC predominance dynamics and infection rates were in general distinct from the mainland. We report here the first known case of Alpha predominance in a Brazilian population, a delay greater than 3 months for the Gamma to dominate the previous variants compared to the mainland, and a faster dispersion rate of Gamma and Delta VOCs compared to the mainland. Phylogenetic analysis revealed the SARS-CoV-2 transmission dynamics in Ilhabela were characterized by multiple independent introduction events of Gamma and Delta, with a few events of Alpha introduction, two of them followed by community transmission. This study evidenced the peculiar behavior of SARS-CoV-2 variants in an isolated population and brought to light the importance of specific programs for SARS-CoV-2 genomic surveillance in isolated populations.     

Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.     

Protective Immunity of the Primary SARS-CoV-2 Infection Reduces Disease Severity Post Re-Infection with Delta Variants in Syrian Hamsters

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Delta variant has evolved to become the dominant SARS-CoV-2 lineage with multiple sub-lineages and there are also reports of re-infections caused by this variant. We studied the disease characteristics induced by the Delta AY.1 variant and compared it with the Delta and B.1 variants in Syrian hamsters. We also assessed the potential of re-infection by these variants in Coronavirus disease 2019 recovered hamsters 3 months after initial infection. The variants produced disease characterized by high viral load in the respiratory tract and interstitial pneumonia. The Delta AY.1 variant produced mild disease in the hamster model and did not show any evidence of neutralization resistance due to the presence of the K417N mutation, as speculated. Re-infection with a high virus dose of the Delta and B.1 variants 3 months after B.1 variant infection resulted in reduced virus shedding, disease severity and increased neutralizing antibody levels in the re-infected hamsters. The reduction in viral load and lung disease after re-infection with the Delta AY.1 variant was not marked. Upper respiratory tract viral RNA loads remained similar after re-infection in all the groups. The present findings show that prior infection could not produce sterilizing immunity but that it can broaden the neutralizing response and reduce disease severity in case of reinfection.     

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2

Background: Since the beginning of the COVID-19 pandemic, several SARS-CoV-2 variants have sequentially emerged. In France, most cases were due to spike D641G-harbouring viruses that descended initially from the Wuhan strain, then by the variant of B.1.160 lineage we called Marseille-4 since the summer of 2020, which was followed by the Alpha and Beta variants in early 2021, then the Delta variant currently. Methods: We determined the neutralising antibody (nAb) titres in sera from convalescent individuals previously infected by these four major local variants and from vaccine recipients to the original Wuhan strain and nine variants, including two recent circulating Delta isolates. Results: The results show high inter-individual heterogeneity in nAbs, especially according to the variant tested. The major variations among nAbs are based on the genotype responsible for the infection. Patients previously infected with the beta and B.1.160 variants had the lowest nAb titres. We show that this heterogeneity is well explained by spike protein mutants modelling using in silico approaches. The highest titres were observed in individuals vaccinated with the Pfizer/BioNTech COVID-19 vaccine, even against the delta variant. Conclusions: Immunity acquired naturally after infection is highly dependent on the infecting variant, and, unexpectedly, mRNA-based vaccine efficacy was shown to be often better than natural immunity in eliciting neutralising antibodies.     

Brief Report: Measuring infectious SARS-CoV-2 in clinical samples reveals a higher viral titer:RNA ratio for Delta and Epsilon vs. Alpha variants

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a challenge to controlling the COVID-19 pandemic. Previous studies indicate that clinical samples collected from individuals infected with the Delta variant may contain higher levels of RNA than previous variants, but the relationship between levels of viral RNA and infectious virus for individual variants is unknown. We measured infectious viral titer (using a microfocus-forming assay) and total and subgenomic viral RNA levels (using RT-PCR) in a set of 162 clinical samples containing SARS-CoV-2 Alpha, Delta, and Epsilon variants that were collected in identical swab kits from outpatient test sites and processed soon after collection. We observed a high degree of variation in the relationship between viral titers and RNA levels. Despite this, the overall infectivity differed among the three variants. Both Delta and Epsilon had significantly higher infectivity than Alpha, as measured by the number of infectious units per quantity of viral E gene RNA (5.9- and 3.0-fold increase; P < 0.0001, P = 0.014, respectively) or subgenomic E RNA (14.3- and 6.9-fold increase; P < 0.0001, P = 0.004, respectively). In addition to higher viral RNA levels reported for the Delta variant, the infectivity (amount of replication competent virus per viral genome copy) may be increased compared to Alpha. Measuring the relationship between live virus and viral RNA is an important step in assessing the infectivity of novel SARS-CoV-2 variants. An increase in the infectivity for Delta may further explain increased spread, suggesting a need for increased measures to prevent viral transmission.     

Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 8.00 and 5.33, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.51-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which, however, might be circumvented by combination therapy with casirivimab together.     

新型冠状病毒(SARS-CoV-2)变异的研究进展

2019年12月底,湖北省武汉市暴发了由新型冠状病毒(SARS-CoV-2)引起的肺炎疫情.迄今为止,该病毒引起的疫情仍在全球流行,累计感染人数超1.8亿.随着SARS-CoV-2在人群间的不断传播,其基因组不断发生变异,从SARS-CoV-2首次出现S蛋白D614G突变到被世界卫生组织列为关切的Alpha、Beta、...     

Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization

The ability of viruses to mutate and evade the human immune system and neutralizing antibodies remains an obstacle to antiviral and vaccine development. Many neutralizing antibodies, including some approved for emergency use authorization (EUA), reduced or lost activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we introduce a geometric deep learning algorithm that efficiently enhances antibody affinity to achieve broader and more potent neutralizing activity against such variants. We demonstrate the utility of our approach on a human antibody P36-5D2, which is effective against SARS-CoV-2 Alpha, Beta, and Gamma but not Delta. We show that our geometric neural network model optimizes this antibody’s complementarity-determining region (CDR) sequences to improve its binding affinity against multiple SARS-CoV-2 variants. Through iterative optimization of the CDR regions and experimental measurements, we enable expanded antibody breadth and improved potency by ∼10- to 600-fold against SARS-CoV-2 variants, including Delta. We have also demonstrated that our approach can identify CDR changes that alleviate the impact of two Omicron mutations on the epitope. These results highlight the power of our deep learning approach in antibody optimization and its potential application to engineering other protein molecules. Our optimized antibodies can potentially be developed into antibody drug candidates for current and emerging SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide over the past 2 y, causing hundreds of millions of confirmed infections and millions of deaths (1). The receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein initiates binding to the host receptor, angiotensin converting enzyme 2 (ACE2) (2–6), and serves as an initial essential step in viral–cell membrane fusion, as well as a potential target for neutralizing antibodies (7–10). Neutralizing antibodies that target RBD have already shown therapeutic and clinical value (11–17).However, reduced sensitivity of SARS-CoV-2 variants to antibody and serum neutralization has been widely observed (18–21). For example, the B.1.617 lineage, also known as the Delta variant, contains two mutations (L452R and T478K) in the RBD that facilitate viral escape—the ability of viruses to evade the immune system and cause disease (22). The L452R mutation is located at the periphery of the receptor binding motif (RBM) and is found to reduce neutralizing activity by antibodies. The T478K mutation in the RBD, located within the epitope region in the RBM, is also associated with antibody escape. There has been striking evidence of antibodies that have been greatly affected, or even have lost their neutralizing activity altogether, by viral escape (23–26).Experimental methods to improve antibody binding and neutralization have been developed. In vitro affinity maturation methods, such as random mutagenesis with display technologies, has been shown to improve antibody binding against target proteins, but such approaches are time consuming and labor intensive (27–32). Targeted optimization toward one particular variant may also result in loss of neutralizing activity against other variants. Efficient optimization of antibodies that confer broad and potent neutralizing activity against diverse variants is therefore urgently needed.Here, we develop and apply a deep learning framework to efficiently optimize antibodies to achieve broader and more potent neutralizing activity against SARS-CoV-2 variants. Based on a large collection of antibody–antigen complex structures and binding affinity data, we trained a geometric neural network model, recently developed in computer vision, that effectively extracts interresidue interaction features and makes predictions of changes in binding affinity due to single or multiple amino acid substitutions to the antigen. To search for favorable complementarity-determining region (CDR) mutations that potentially improve antibody binding, we also simulate an in silico ensemble of predicted complex structures with CDR mutations to obtain a robust estimation of the free energy change, also known as ΔΔG. Compared to traditional approaches, the deep learning search space is theoretically much larger and is also easily applicable in targeting multiple variants simultaneously via multiobjective optimization.To demonstrate the utility of our approach, we sought to optimize a human neutralizing antibody P36-5D2, which was initially isolated from a convalescent patient, and demonstrated reasonably strong potency and breadth against Alpha, Beta, and Gamma (33) but not Delta, due to Delta’s L452R but not T478K mutation through computational structure analysis. We applied our deep learning model to predict CDR sequences that potentially improved binding affinity against the Delta variant while maintaining activity against Alpha, Beta, and Gamma. Through an iterative process of modeling and experimental validation, we were able to obtain six optimized antibodies with substantially improved potency of about 10- to 600-fold against multiple variants, including Delta. We also provide initial promising studies on Omicron. These results highlight the power of deep learning approaches for antibody optimization and their potential application to a wide range of other protein molecules. The optimized antibodies presented here also have the potential to be further developed as antibody drug candidates against SARS-CoV-2 variants.     

Longitudinal Analysis of Coronavirus-Neutralizing Activity in COVID-19 Patients

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has now been continuing for more than two years. The infection causes COVID-19, a disease of the respiratory and cardiovascular system of variable severity. Here, the humoral immune response of 80 COVID-19 patients from the University Hospital Frankfurt/Main, Germany, was characterized longitudinally. The SARS-CoV-2 neutralization activity of serum waned over time. The neutralizing potential of serum directed towards the human alpha-coronavirus NL-63 (NL63) also waned, indicating that no cross-priming against alpha-coronaviruses occurred. A subset of the recovered patients (n = 13) was additionally vaccinated with the mRNA vaccine Comirnaty. Vaccination increased neutralization activity against SARS-CoV-2 wild-type (WT), Delta, and Omicron, although Omicron-specific neutralization was not detectable prior to vaccination. In addition, the vaccination induced neutralizing antibodies against the more distantly related SARS-CoV-1 but not against NL63. The results indicate that although SARS-CoV-2 humoral immune responses induced by infection wane, vaccination induces a broad neutralizing activity against multiple SARS-CoVs, but not to the common cold alpha-coronavirus NL63.     

SARS-CoV-2 Omicron variant BA.2 neutralisation in sera of people with Comirnaty or CoronaVac vaccination,infection or breakthrough infection,Hong Kong, 2020 to 2022

BackgroundOmicron subvariant BA.2 circulation is rapidly increasing globally.AimWe evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.MethodsUsing 50% plaque reduction neutralisation tests (PRNT₅₀), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.ResultsIn vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT₅₀ titres were comparable but significantly (p < 10 ^− 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT₅₀ titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT₅₀ titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.ConclusionsExisting vaccines can be of help against the BA.2 subvariant.     

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.     

SARS-CoV-2 Delta Variant Pathogenesis and Host Response in Syrian Hamsters

B.1.617 is becoming a dominant Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) lineage worldwide with many sublineages, of which B.1.617.2 is designated as a variant of concern. The pathogenicity of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 was evaluated and compared with that of B.1, an early virus isolate with D614G mutation in a Syrian hamster model. Viral load, antibody response, and lung disease were studied. There was no significant difference in the virus shedding pattern among these variants. High levels of SARS-CoV-2 sub genomic RNA were detected in the respiratory tract of hamsters infected with the Delta variant for 14 days, which warrants further transmission studies. The Delta variant induced lung disease of moderate severity in about 40% of infected animals, which supports the attributed disease severity of the variant. Cross neutralizing antibodies were detected in animals infected with B.1, Delta, and B.1.617.3 variant, but neutralizing capacity was significantly lower with B.1.351 (Beta variant).