Wuhan Virus Research Articles

Virulence and tissue tropism of different epidemiologically significant SARS-CoV-2 variants for golden Syrian hamsters

Introduction. Animal models for SARS-CoV-2 infection, reproducing the clinical features of COVID-19 in humans, are important tools for studying the pathogenesis of the disease, transmission of the pathogen and are indispensable for testing antiviral drugs and vaccines. The aim of the study was to assess the virulence and tissue tropism for golden Syrian hamsters of SARS-CoV-2 strains belonging to different epidemiologically significant variants: Wuhan-like, Delta, Omicron BA.1.1 and Omicron BA.5.2. Materials and methods. Hamsters were intranasally infected with different SARS-CoV-2 strains. Virulence and tissue tropism of SARS-CoV-2 strains were assessed by comparing the dynamics of weight, viral load in organs and histopathological changes in lungs in infected and uninfected animals. Results. The Wuhan-like Dubrovka strain had the greatest virulence for hamsters, which was manifested by the development of severe pneumonia and a delay in weight gain by 14.6%, high virus content in the lungs, nasal passages and brain — 6.2, 5,9 and 3.7 lg TCID50/ml of homogenate, respectively. Presumably, it was the infection of the Wuhan-like virus of the central nervous system that negatively affected the weight and general condition of the animals. When hamsters were infected with viruses belonging to the Delta and Omicron variants, the observed minor weight loss in animals was uninformative, so indicators such as lung histopathology, viral load in the lungs, nasal passages, heart and other organs played a decisive role in assessing the virus pathogenicity. A score assessment of lung histopathology was of particular value in assessing the severity of pneumonia, since it reduced subjectivity in evaluating the results of histological examination and provided a semi-quantitative assessment of the pathological process. Conclusion. Despite the revealed lower virulence for hamsters of viruses belonging to the Delta and Omicron variants compared to the ancestral Wuhan virus, this animal model for COVID-19 retains its value for conducting preclinical trials of antiviral drugs.

Development and characterization of a multimeric recombinant protein using the spike protein receptor binding domain as an antigen to induce SARS-CoV-2 neutralization.

SARS-CoV2 virus, responsible for the COVID-19 pandemic, has four structural proteins and 16 nonstructural proteins. S-protein is one of the structural proteins exposed on the virus surface and is the main target for producing neutralizing antibodies and vaccines. The S-protein forms a trimer that can bind the angiotensin-converting enzyme 2 (ACE2) through its receptor binding domain (RBD) for cell entry. The goal of this study was to express in HEK293 cells a new RBD recombinant protein in a constitutive and stable manner in order to use it as an alternative immunogen and diagnostic tool for COVID-19. The protein was designed to contain an immunoglobulin signal sequence, an explanded C-terminal section of the RBD, a region responsible for the bacteriophage T4 trimerization inducer, and six histidines in the pCDNA-3.1 plasmid. Following transformation, the cells were selected with geneticin-G418 and purified from serum-fre culture supernatants using Ni2+-agarand size exclusion chromatography. The protein was structurally identified by cross-linking and circular dichroism experiments, and utilized to immunize mice in conjuction with AS03 or alum adjuvants. The mice sera were examined for antibody recognition, receptor-binding inhibition, and virus neutralization, while spleens were evaluated for γ-interferon production in the presence of RBD. The protein released in the culture supernatant of cells, and exhibited a molecular mass of 135 kDa with a secondary structure like the monomeric and trimeric RBD. After purification, it formed a multimeric structure comprising trimers and hexamers, which were able to bind the ACE2 receptor. It generated high antibody titers in mice when combined with AS03 adjuvant (up to 1:50,000). The sera were capable of inhibiting binding of biotin-labeled ACE2 to the virus S1 subunit and could neutralize the entry of the Wuhan virus strain into cells at dilutions up to 1:2000. It produced specific IFN-γ producing cells in immunized mouse splenocytes. Our data describe a new RBD containing protein, forming trimers and hexamers, which are able to induce a protective humoral and cellular response against SARS-CoV2. These results add a new arsenal to combat COVID-19, as an alternative immunogen or antigen for diagnosis.

Designing of multi-Epitope vaccine against spike glycoprotein of SARS-CoV-2 using immunoinformatics approach

BackgroundCOVID-19 caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome) has created an alarming situation worldwide. The surface (S) glycoprotein of novel coronavirus, encoded by the genome of SARS-CoV-2, plays an role in attachment, fusion as well as entry into the host cell. The spike glycoprotein plays vital role in not only infection but pathogenesis and adaptive immunity, and, therefore, the S glycoprotein is considered as the main target for the development of effective and durable vaccine against SARS-CoV-2. Present study aims to compare the SARS-CoV-2 spike sequence obtained from first Wuhan virus with those of Asian SARS-CoV-2 isolates. ResultA total of 1165 mutations from 657 sequences of Asia submitted in the month of November 2020 to February 2021 were detected. Further, secondary structure prediction followed by protein modeling analysis was performed which revealed, these mutations, considerably altered the stability of Spike protein. Additionally, Physiochemical properties, toxicity, allergenicity and stability of spike glycoprotein were estimated to demonstrate the specificity of the epitope candidates. Subsequently, we identified a total of 34B-cell and 10 T-cell immune epitopes. Among the predicted epitopes, 26 B-cell and 9T-cell epitopes showed non-allergenic, non-toxic and highly antigenic properties. ConclusionTaken together, our study showed spike glycoprotein of SARS-CoV-2 can be a potentially good candidate for the development of vaccine to curb SARS-CoV-2 infections.

Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies.

The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment of COVID-19 with anti-coronaviral neutralizing antibodies. The latest viral variants demonstrate pronounced resistance to the vast majority of human monoclonal antibodies raised against the ancestral Wuhan variant. Less is known about the susceptibility of the evolved virus to camelid nanobodies developed at the start of the pandemic. In this study, we compared nanobody repertoires raised in the same llama after immunization with Wuhan's RBD variant and after subsequent serial immunization with a variety of RBD variants, including that of SARS-CoV-1. We show that initial immunization induced highly potent nanobodies, which efficiently protected Syrian hamsters from infection with the ancestral Wuhan virus. These nanobodies, however, mostly lacked the activity against SARS-CoV-2 omicron-pseudotyped viruses. In contrast, serial immunization with different RBD variants resulted in the generation of nanobodies demonstrating a higher degree of somatic mutagenesis and a broad range of neutralization. Four nanobodies recognizing distinct epitopes were shown to potently neutralize a spectrum of omicron variants, including those of the XBB sublineage. Our data show that nanobodies broadly neutralizing SARS-CoV-2 variants may be readily induced by a serial variant RBD immunization.

High-resolution map of the Fc functions mediated by COVID-19-neutralizing antibodies.

A growing body of evidence shows that fragment crystallizable (Fc)-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc functions. Surprisingly, we found that nAbs with the most potent Fc function recognize the N-terminal domain, followed by those targeting class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc functions. The divergent properties of the neutralizing and Fc function-mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc functions of polyclonal sera differ from the profile observed with nAbs, suggesting that non-neutralizing antibodies also contribute to Fc functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies, and the evaluation of correlates of protection.

Soft Power and Vaccine Diplomacy: An Analysis of China's Global Image Enhancement during the COVID-19 Pandemic

The COVID-19 pandemic amplified global rivalries. The US blamed China for the viral outbreak in Wuhan. Many in the US, including former President Trump and his aides, called the Coronavirus the “Chinese Virus” or the “Wuhan virus,” raising anti-Chinese sentiments in the West. At the same time, Beijing sought to use this opportunity to practice its vaccine diplomacy to shore up its international stature as a world power amid the pandemic. In this pursuit, China provided vaccines and personal protective equipment (PPEs) as global public goods, particularly to the global South. Using both primary and secondary sources and relying on a mixed approach for data analysis, this paper analyzes the effectiveness of China’s vaccine diplomacy during Covid-19. It explores China’s use of soft power through social media, including infodemics and ‘twiplomacy’ to bolster its image. The article also assesses the role of China’s ‘wolf warrior diplomacy’ that manipulated the facts to advance its propaganda. Conclusively, this paper argues that Chinese vaccine diplomacy served as an effective tool to enhance China’s global image as a responsible great power, albeit undermined through tactics such as the manipulation of information.

Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin®)

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

Anti-Asian Media Labeling in the COVID-19 Pandemic: The Role of Social Identity and Information Accuracy

This study examines the roles of sports fan identity and political affiliation on the perceived accuracy of mediated information during a global pandemic, which adversely affected the sports world through national and international league stoppages and newly developed health and safety protocols. A 4 (news source) × 3 (pandemic term) experimental design was incorporated. 420 subjects read one of twelve factually accurate sports articles but with differing media outlets (MSNBC, Fox News, Associated Press, Bleacher Report) and pandemic terminology of differing anti-Asian sentiments (COVID-19, Chinese coronavirus, Wuhan Virus). Results demonstrated that manipulation of media source and pandemic term did not influence perceived information accuracy, but that one’s social identification did alter results. Shifts in media accuracy depended on whether facts were incongruent with one’s identity, while xenophobic language was more likely to be accepted if the information came from an acceptable and parallel media source. Ramifications for journalism ethics and media literacy are offered, highlighting the increased role one’s identity has in information processing in modern media.

Omicron infection-associated T- and B-cell immunity in antigen-naive and triple-COVID-19-vaccinated individuals.

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2-3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.

The Influence of Different SARS-CoV-2 Strains on Changes in Maximal Oxygen Consumption, Ventilatory Efficiency and Oxygen Pulse of Elite Athletes.

The aim of this study was to evaluate the influence of different SARS-CoV-2 strains on the functional capacity of athletes. In total, 220 athletes underwent cardiopulmonary exercise testing (CPET) after coronavirus infection and before returning to sports activities. Eighty-eight athletes were infected by the Wuhan virus, and 66 were infected during the Delta and Omicron strain periods of the pandemic. The CPET results showed significantly decreased maximal oxygen consumption, ventilatory efficiency, and oxygen pulse in athletes who were infected with Wuhan and Delta strains compared to athletes who suffered from Omicron virus infection. An early transition from aerobic to anaerobic metabolic pathways for energy production was observed in the Wuhan and Delta groups but not in athletes who were infected with the Omicron strain. There were no differences in the obtained results when Wuhan and Delta virus variants were compared. These results suggest that the Wuhan and Delta virus strains had a significantly greater negative impact on the functional abilities of athletes compared to the Omicron virus variant, especially in terms of aerobic capacity and cardiorespiratory function.

The Prevalence of Herding in Indian Auto Sector: Implications for Market Efficiency

The worldwide catastrophes due to the spread of Wuhan virus, India had witnessed an explosive change in the economic activity, mainly in the investment pattern. This made the investors to do panic trading by following what others were doing in the market. We offer an empirical analysis to examine the presence of herding in Indian Automobile Sector during pre-pandemic and pandemic period (COVID-19). To detect the presence of herding, we applied Cross Sectional Absolute Deviation (CSAD) and One-way ANOVA was employed to examine whether there is any significant difference in the auto index during Pre pandemic and pandemic period. The result shows that herding behaviour is driven by panic and shocks during the pandemic period. However, herding is not prevalent during the pre-pandemic and whole period. This paper concludes that the Indian market is efficient unless there is any panic or fear among the investors.

What makes the Wuhan virus American?

From the sociolinguistic perspective, conspiracy theories (CT), which convey heterodox forms of knowledge that diverge from accepted narratives, are worth examining since their discourses abound in persuasive language. Still, the discourse of CTs is under-researched (Demata/Zorzi/ Zottola 2022). The present empirical, discourse-analytical case study seeks to address this lacuna by exploring the discursive (de)legitimation strategies of conspiracy discourse in competing narrative frames. The research adopted the Critical Discourse Analysis (CDA) perspective, and the comparative analysis was carried out within the methodological framework developed by van Leeuwen (2008) and Tankard (2001). The findings complement van Leeuwen’s “grammar of legitimation”, and also contribute to existing knowledge on framing theories. The results of the explorative case study indicate that the persuasiveness of the discursive strategies of (de)legitimisation depends on several features, such as synergy, projection, the sense of belonging, silencing with blockers, implying the generality of specific cases, and the partial investigation of causality.

Microbead-based extracorporeal immuno-affinity virus capture: a feasibility study to address the SARS-CoV-2 pandemic

In this paper, we report on the utilization of micro-technology based tools to fight viral infections. Inspired by various hemoperfusion and immune-affinity capture systems, a blood virus depletion device has been developed that offers highly efficient capture and removal of the targeted virus from the circulation, thus decreasing virus load. Single-domain antibodies against the Wuhan (VHH-72) virus strain produced by recombinant DNA technology were immobilized on the surface of glass micro-beads, which were then utilized as stationary phase. For feasibility testing, the virus suspension was flown through the prototype immune-affinity device that captured the viruses and the filtered media left the column. The feasibility test of the proposed technology was performed in a Biosafety Level 4 classified laboratory using the Wuhan SARS-CoV-2 strain. The laboratory scale device actually captured 120,000 virus particles from the culture media circulation proving the feasibility of the suggested technology. This performance has an estimated capture ability of 15 million virus particles by using the therapeutic size column design, representing three times over-engineering with the assumption of 5 million genomic virus copies in an average viremic patient. Our results suggested that this new therapeutic virus capture device could significantly lower virus load thus preventing the development of more severe COVID-19 cases and consequently reducing mortality rate.Graphical

Emergence of a New Creutzfeldt-Jakob Disease: 26 Cases of the Human Version of Mad-Cow Disease, Days After a COVID-19 Injection

Creutzfeldt-Jakob Disease, the formerly rare but universally fatal prion disease in humans, normally progresses over several decades before it leads to death. In the Appendix to this paper, we highlight the presence of a prion region in the spike protein of the original SARS-CoV-2, and in all the “vaccine” variants built from the Wuhan virus. The prion region in the spike of SARS-CoV-2 has a density of mutations eight times greater than that of the rest of the spike, and, yet, strangely that entire prion region disappears completely in the Omicron variant. In the main body of our text, we present 26 cases of Creuzfeldt-Jacob Disease, all diagnosed in 2021 with the first symptoms appearing within an average of 11.38 days after a Pfizer, Moderna, or AstraZeneca COVID-19 injection. Because the causal progression, the etiopathogenesis, of these atypical and new cases of human prion disease — cases of what is apparently a totally new form of rapidly developing Creuzfeldt-Jacob Disease — we focus on the chronology of the symptomatic development. We consider it from an anamnestic point of view — one in which we compare the typical development of pre-COVID cases of Creuzfeldt-Jacob Disease to the extremely accelerated development of similar symptoms in the 26 cases under examination. By such an approach, we hope to work out the etiopathogenesis critical to understanding this new and much more rapidly developing human prion disease. By recalling the sequential pathway of that the formerly subacute and slowly developing disease followed in the past, and by comparing it with this new, extremely acute, rapidly developing prion disease — one following closely after one or more of the COVID-19 injections — we believe it is correct to infer that the injections caused the disease in these 26 cases. If so, they have probably also caused a many other cases that have gone undiagnosed because of their rapid progression to death. By late 2021, 20 had died within 4.76 months of the offending injection. Of those, 8 died suddenly within 2.5 months confirming the rapid progression of this accelerated form of Creuzfeldt-Jacob Disease. By June 2022, 5 more patients had died, and at the time of this current writing, only 1 remains still alive.

An ultrastructural and genomic study on the SARS-CoV-2 variant B.1.210 circulating during the first wave of COVID-19 pandemic in India

PurposeThe study aims to isolate and understand cytopathogenesis, ultrastructure, genomic characteristics and phylogenetic analysis of SARS-CoV-2 virus of B.1.210 lineage, that circulated in India during first wave of the pandemic. MethodsClinical specimen from an interstate traveller from Maharashtra to Karnataka, in May 2020, who was positive by RT PCR for SARS-CoV-2 infection was subjected to virus isolation and Whole Genome Sequencing. Vero cells were used to study cytopathogenesis and ultrastructural features by Transmission Electron Microscopy (TEM). Phylogenetic analysis of the whole genome sequences of several SARS-CoV-2 variants downloaded from GISAID was performed in comparison with the B.1.210 variant identified in this study. ResultsThe virus was isolated in Vero cells and identified by immunofluorescence assay and RT PCR. The growth kinetics in infected Vero cells revealed a peak viral titre at 24 ​h post-infection. Ultrastructural studies revealed distinct morphological changes with accumulation of membrane-bound vesicles containing pleomorphic virions in the cytoplasm, with single or multiple intranuclear filamentous inclusions and dilated rough endoplasmic reticulum with viral particles. Whole genome sequence of the clinical specimen as well as the isolated virus revealed the virus to be of lineage B.1.210 with the D614G mutation in the spike protein. Phylogenetic analysis of the whole genome sequence in comparison with other variants reported globally revealed that the isolated SARS-CoV-2 virus of lineage B.1.210 is closely related to the original Wuhan virus reference sequence. ConclusionsThe SARS-CoV-2 variant B.1.210 virus isolated here showed ultrastructural features and cytopathogenesis similar to that of the virus reported during early phase of pandemic. Phylogenetic analysis showed that the isolated virus is closely related to the original Wuhan virus, thereby suggesting that the SARS-CoV-2 lineage B.1.210 that was circulating in India during the early phase of pandemic is likely to have evolved from the original Wuhan strain.

Omicron-specific mRNA vaccine induced cross-protective immunity against ancestral SARS-CoV-2 infection with low neutralizing antibodies.

The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. To overcome this, an Omicron-specific messenger RNA(mRNA) vaccine was designed. The extracellular domain of the spike of the Omicron variant was fused with a modified GCN4 trimerization domain with low immunogenicity (TSomi). After immunization with TSomi mRNA in hamsters, animals were challenged with SARS-CoV-2 virus. The raised nonneutralizing antibodies or cytokine secretion responses can recognize both Wuhan S and Omicron S. However, the raised antibodies neutralized SARS-CoV-2 Omicron virus infection but failed to generate Wuhan virus neutralizing antibodies. Surprisingly, TSomi mRNA immunization protected animals from Wuhan virus challenge. These data indicated that non-neutralizing antibodies or cellular immunity may play a more important role in vaccine-induced protection than previously believed. Next-generation COVID-19 vaccines using the Omicron S antigen may provide sufficient protection against ancestral or current SARS-CoV-2 variants.

THE CORONA PANDEMIC STORY : WHEN HOPE APPEARED ELUSIVE BY GEORGEMBURU

The author undertakes a descriptive and synthesis and analysis of the novel Covid19 Pandemic dubbed as the Corona disease or the “Wuhan Virus”. Essentially, the author explores six objectives and points to the effects of the pandemic psychologically, health-wise, economically and even socially. Quint essentially, the author contends the untold value of prior planning in disaster preparedness and mitigation, a glaring challenge to all nations across the globe. Thirdly, the need for research as well as integrity and being resolute and for the right in the wake of disasters is being highlighted. The paper also highlights some statistical on the continuous rise and trends of the Covid19 which started in China in November 2019 spreading into all continents and most countries the world over. Towards the end vital lessons have been pointed out and recommendation made on the need form or research, impressing the need for the input of the key players and or stakeholders in response and mitigation of such a pandemic no wand in the future.

The medicalisation of threats, immigration as contagion, and White supremacy in an age of terror

ABSTRACT The 6 January 2021 events must be analysed within a broader context than the phenomenon of Trumpism. The attempted coup that brought together (former) members of the military, White supremacist organisations, and regular citizens has a rich genealogy. We trace this genealogy to the events of 11 September 2001 and the homeland security state built in their wake, even as its reach extends further into U.S. history. Post-9/11 discourse became a mechanism for seeking and interpreting perceived threats to the United States and its citizens. Through it, immigration, disease, and White supremacy became intertwined. Perceptions of infectious and biological threats became racialised. With the emergence of the novel coronavirus, President Trump enacted travel bans and routinely referred to the virus as the “Wuhan virus” or “Chinese virus.” Hate crimes against Asians and Asian Americans followed, as this language reinvigorated Orientalist histories. We examine rhetoric about disease over the past twenty years, particularly as it has reinforced militarism and White supremacy, all against the backdrop of 9/11. State constructions of 9/11 and 9/11 memory inform and explain our recent and contemporary terrain.

Immunological study of COVID-19 vaccine candidate based on recombinant spike trimer protein from different SARS-CoV-2 variants of concern.

The emergency of new SARS-CoV-2 variants that feature increased immune escape marks an urgent demand for better vaccines that will provide broader immunogenicity. Here, we evaluated the immunogenic capacity of vaccine candidates based on the recombinant trimeric spike protein (S) of different SARS-CoV-2 variants of concern (VOC), including the ancestral Wuhan, Beta and Delta viruses. In particular, we assessed formulations containing either single or combined S protein variants. Our study shows that the formulation containing the single S protein from the ancestral Wuhan virus at a concentration of 2µg (SW2-Vac 2µg) displayed in the mouse model the highest IgG antibody levels against all the three (Wuhan, Beta, and Delta) SARS-CoV-2 S protein variants tested. In addition, this formulation induced significantly higher neutralizing antibody titers against the three viral variants when compared with authorized Gam-COVID-Vac-rAd26/rAd5 (Sputnik V) or ChAdOx1 (AstraZeneca) vaccines. SW2-Vac 2µg was also able to induce IFN-gamma and IL-17, memory CD4 populations and follicular T cells. Used as a booster dose for schedules performed with different authorized vaccines, SW2-Vac 2µg vaccine candidate also induced higher levels of total IgG and IgG isotypes against S protein from different SARS-CoV-2 variants in comparison with those observed with homologous 3-dose schedule of Sputnik V or AstraZeneca. Moreover, SW2-Vac 2µg booster induced broadly strong neutralizing antibody levels against the three tested SARS-CoV-2 variants. SW2-Vac 2µg booster also induced CD4+ central memory, CD4+ effector and CD8+ populations. Overall, the results demonstrate that SW2-Vac 2 µg is a promising formulation for the development of a next generation COVID-19 vaccine.

Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis.

The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1β in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1β correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization.HighlightsMucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1β correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.