Search

Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination 1,2 . The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Hand, foot, and mouth disease (HFMD) is a common childhood infection caused by human enteroviruses and is clinically characterised by fever with vesicular rash on the hands, feet, and mouth. While enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) were the major etiological agents of HFMD in India earlier, the data on recently circulating enteroviruses associated with HFMD are sparse. Here, we describe the molecular epidemiology of enteroviruses associated with HFMD in South India from 2015 to 2017. We used archived enterovirus real-time reverse transcription (RT) PCR-positive vesicle swab and/or throat swab specimens from clinically suspected HFMD cases collected from four secondary-care hospitals in South India between July 2015 and December 2017. PCR amplification and sequencing were done based on the 5'VP1, 3'VP1, VP2, or 5´NCR regions to identify enterovirus types. Genetic diversity among enteroviruses was inferred by phylogenetic analysis. Of the 107 enterovirus RNA real-time RT-PCR-positive HFMD cases, 69 (64%) were typed as CVA6, 16 (15%) were CVA16, and one (1%) was CVA10, whereas in 21 (20%) cases, the virus was not typeable by any of the methods used in the study. The majority of HFMD cases (89, 83%) were in children less than five years old, while 11 (10.3%) were in adults. 5'VP1 yielded the maximum number of enteroviruses genotyped, and phylogenetic analysis showed that the CVA6 strains belonged to subclade D3, while the subclades of CVA16 and CVA10 were B1c and D, respectively. The predominant etiological agent of HFMD in South India during 2015-2017 was CVA6, followed by CVA16 and CVA10., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)