BBIBP-CorV Vaccination against the SARS-CoV-2 Virus Affects the Gut Microbiome.

Several observational studies have confirmed that the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) might substantially affect the gastrointestinal (GI) system by replicating in human small intestine enterocytes. Yet, so far, no study has reported the effects of inactivated SARS-CoV-2 virus vaccines on gut microbiota alterations. In this study, we examined the effects of the BBIBP-CorV vaccine (ChiCTR2000032459, sponsored by the Beijing Institute of Biological Products/Sinopharm), on gut microbiota. Fecal samples were collected from individuals whoreceived two doses of intramuscular injection of BBIBP-CorV and matched unvaccinated controls. DNA extracted from fecal samples was subjected to 16S ribosomal RNA sequencing analysis. The composition and biological functions of the microbiota between vaccinated and unvaccinated individuals were compared. Compared with unvaccinated controls, vaccinated subjects exhibited significantly reduced bacterial diversity, elevated firmicutes/bacteroidetes (F/B) ratios, a tendency towards Faecalibacterium-predominant enterotypes, and altered gut microbial compositions and functional potentials. Specifically, the intestinal microbiota in vaccine recipients was enriched with Faecalibacterium and Mollicutes and with a lower abundance of Prevotella, Enterococcus, Leuconostocaceae, and Weissella. Microbial function prediction by phylogenetic investigation of communities using reconstruction of unobserved states (PICRUSt) analysis further indicated that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in carbohydrate metabolism and transcription were positively associated with vaccine inoculation, whereas capacities in neurodegenerative diseases, cardiovascular diseases, and cancers were negatively affected by vaccines. Vaccine inoculation was particularly associated with gut microbiota alterations, as was demonstrated by the improved composition and functional capacities of gut microbiota.

Alterations of Fecal Metabolome Associated with BBIBP-CorV Vaccines against the SARS-CoV-2 Virus.

BACKGROUND: The SARS-CoV-2 vaccine has been implemented in response to the 2019 Coronavirus Disease (COVID-19) pandemic worldwide. Dysregulation of gut metabolite is associated with COVID-19 patients. However, the effect of vaccination on the gut metabolite remains unknown, and it is critical to investigate the shifts in metabolic profiles following vaccine treatment. METHODS: In the present study, we conducted a case-control study to assess the fecal metabolic profiles between individuals who received two doses of intramuscular injection of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) (n = 20), and matched unvaccinated controls (n = 20) using untargeted gas chromatography and time-of-flight mass spectrometry (GC-TOF/MS). RESULTS: Significant different metabolic profiles were observed between subjects receiving SARS-CoV-2 virus vaccines and the unvaccinated. Among a total of 243 metabolites from 27 ontology classes identified in the study cohort, 64 metabolic markers and 15 ontology classes were dramatically distinct between vaccinated and unvaccinated individuals. There were 52 enhanced (such as Desaminotyrosine, Phenylalanine) and 12 deficient metabolites (such as Octadecanol, 1-Hexadecanol) in vaccinated individuals. Along with altered metabolic compositions, multiple functional pathways in Small MoleculePathway Database (SMPDB) and Kyoto Encyclopedia of Genes and Genomes (KEGG) varied between groups. Our results indicated that urea cycle; alanine, aspartate, and glutamate metabolism; arginine and proline metabolism; phenylalanine metabolism and tryptophan metabolism were abundant after vaccination. Additionally, correlation analysis showed that intestinal microbiome was related to alteration in metabolite composition and functions. CONCLUSIONS: The present study indicated the alterations in the gut metabolome after COVID-19 vaccination and the findings provide a valuable resource for in-depth exploration of mechanisms between gut metabolite and SARS-CoV-2 virus vaccines.

Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.

SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1-BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.

Characterization of the Intestinal Microbiome in Healthy Adults over Sars-Cov-2 Vaccination.

BACKGROUND: In response to the outbreak of coronavirus disease 2019 (COVID-19) worldwide, inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are implemented. Dysbiosic gut microbiota is implicated in the COVID-19 patients. Whereas, how intestinal microbiota are affected by vaccination remains elusive, and it is important to investigate the microbial shifts during vaccines treatment. METHODS: In the present study, we assessed the gut microbial composition in healthy adults, and performed comparison before and post an inactivated SARS-CoV-2 vaccine candidate, BBIBP-CorV vaccination. RESULTS: Microbial diversity in shannon, pielou evenness, simpson and invsimpson index was remarkably suppressed by vaccination. Ruminococcus and Actinomyces were observed to be strikingly deficient, and Faecalibacterium was dramatically augmented after BBIBP-CorV treatment. Potential functional profiles of gut microbiome in amino acid metabolism, lipid biosynthesis proteins and steroid biosynthesis were remarkably increased, while the capacity in renin-angiotensin system was remarkably decreased following vaccines. CONCLUSIONS: Our study suggests that inactivated BBIBP-CorV against SARS-CoV-2 could elicit modulations on gut microbial composition and functions, which might favor host immune response and protect from COVID-19.

Structure and function analysis of a potent human neutralizing antibody CA521FALA against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521FALA, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521FALA showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521FALA also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521FALA inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521FALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521FALA blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521FALA a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.