During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including 3
rd
dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is less after infection compared to all vaccines evaluated, but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks post-vaccination in some cases. SARS-CoV-2 antibody specificity, breadth and maturation are affected by imprinting from exposure history, and distinct histological and antigenic contexts in infection compared to vaccination.
Highlights d Antibodies to four COVID-19 vaccines differed in an observational study in Mongolia d Responses from high to low: Pfizer/BioNTech > AstraZeneca > Sputnik V > Sinopharm d Breakthrough infections in June to early July of 2021 were due mostly to the Alpha variant d After breakthrough infection, high antibody levels are seen in all vaccine groups
Background:
Mongolia is a highly endemic region for chronic hepatitis B (HBV), hepatitis delta (HDV), and hepatitis C (HCV) infections. Aim of this study was to comprehensively characterize chronic viral hepatitis among Mongols living in Southern California.
Methods:
Three screening events were conducted between August to November 2018, with 528 adult Mongols tested for HBV and HCV. HBsAg (+) individuals (CHB) underwent additional testing for HDV RNA and anti-HDV. Liver tests, platelet count and FibroScan™ were performed on CHB and chronic HCV (CHC) individuals.
Results:
51/534 were HBsAg reactive (9.7%) and all were foreign born. Mean age of CHB individuals was 37.8 (range 18–69) years. 46/51 were HBeAg (−). HBV genotypes were exclusively D2 or A1. 21/51 (41.2%) were anti-HDV (+) and 17/51 (33.3%) were HDV-RNA (+). HDV RNA (+) individuals had significantly higher ALT, Fibrosis-4 score and liver stiffness compared to HDV RNA (−) individuals. Incidence of advanced fibrosis was higher in HDV RNA (+) individuals (57% vs. 13%, p=0.013). 48 (9.1%) individuals were anti-HCV (+) and 19 (3.6%) were HCV RNA (+). Mean age of CHC individuals was 40.2 (range 28–71) years. Prevalence of anti-HCV (+) was higher among those born between 1945–1965 versus those born after 1965 (18.8% vs 7.9%, p=0.025). Genotype 1b was predominant. Incidence of cirrhosis was 7% among all participants.
Conclusions:
Mongols living in the US are at high risk for CHB and CHC infections. One-third of CHB individuals had CHD super-infection with advanced fibrosis. Universal screening for viral hepatitis in Mongols in the U.S. is mandatory.
A surge in Covid-19 cases in Mongolia in March 2021 resulted in a government-mandated shutdown. This shutdown was relaxed in May 2021 as case numbers decreased and nationwide vaccination rates using Sinopharm, Covishield/AstraZeneca, Sputnik V, and Pfizer/BioNTech vaccines exceeded 50% of the population. Case rates increased again in early June 2021 in both vaccinated and non-vaccinated individuals. To determine whether the surge was due to the emergence of Delta or another variant, or vaccine failure, a rapid, opportunistic investigation was conducted that comprised virus sequence analysis of nasal swab samples from breakthrough cases and antibody assays of plasma from healthy vaccinees. More than 90% of breakthrough infections during the second case surge were due to the Alpha variant. Spike protein ELISA and SARS-CoV-2 neutralization assays data revealed large differences in plasma titers of antibodies to SARS-CoV-2, with mRNA vaccines eliciting higher titers than adenovirus-vectored or killed virus vaccines.
Author Contributions: Drs N.J. Dashdorj and N. Mishra had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Lipkin and N. Mishra contributed equally to this work.
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