Rotavirus vaccine-derived cases in Belgium: Evidence for reversion of attenuating mutations and alternative causes of gastroenteritis
Autor: | Ceren Simsek, Mandy Bloemen, Daan Jansen, Patrick Descheemaeker, Marijke Reynders, Marc Van Ranst, Jelle Matthijnssens |
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Rok vydání: | 2022 |
Předmět: |
NOROVIRUS
Rotavirus Genotype HOST-RANGE RESTRICTION Immunology PROTEIN INFANTS CHILDREN Research & Experimental Medicine Rotavirus Infections MULTIPLE SEQUENCE ALIGNMENT Belgium Humans Acute gastroenteritis Antigens Viral Phylogeny Science & Technology General Veterinary General Immunology and Microbiology STRAINS Rotavirus Vaccines Public Health Environmental and Occupational Health Infant Co-infection Gastroenteritis qPCR Infectious Diseases Medicine Research & Experimental NEUTRALIZATION NGS VP4 Mutation VIRUS Molecular Medicine Life Sciences & Biomedicine Rotavirus vaccine |
Zdroj: | Vaccine. 40:5114-5125 |
ISSN: | 0264-410X |
DOI: | 10.1016/j.vaccine.2022.06.082 |
Popis: | Since the introduction of live-attenuated rotavirus vaccines in Belgium in 2006, surveillance has routinely detected rotavirus vaccine-derived strains. However, their genomic landscape and potential role in gastroenteritis have not been thoroughly investigated. We compared VP7 and VP4 nucleotide sequences obtained from rotavirus surveillance with the Rotarix vaccine sequence. As a result, we identified 80 vaccine-derived strains in 5125 rotavirus-positive infants with gastroenteritis from 2007 to 2018. Using both viral metagenomics and reverse transcription qPCR, we evaluated the vaccine strains and screened for co-infecting enteropathogens. Among the 45 patients with known vaccination status, 39 were vaccinated and 87% received the vaccine less than a month before the gastroenteritis episode. Reconstruction of 30 near complete vaccine-derived genomes revealed 0-11 mutations per genome, with 88% of them being non-synonymous. This, in combination with several shared amino acid changes among strains, pointed at selection of minor variant(s) present in the vaccine. We also found that some of these substitutions were true revertants (e.g., F167L on VP4, and I45T on NSP4). Finally, co-infections with known (e.g., Clostridioides difficile and norovirus) and divergent or emerging (e.g., human parechovirus A1, salivirus A2) pathogens were detected, and we estimated that 35% of the infants likely had gastroenteritis due to a 'non-rotavirus' cause. Conversely, we could not rule out the vaccine-derived gastroenteritis in over half of the cases. Continued studies inspecting reversion to pathogenicity should monitor the long-time safety of live-attenuated rotavirus vaccines. All in all, the complementary approach with NGS and qPCR provided a better understanding of rotavirus vaccine strain evolution in the Belgian population and epidemiology of co-infecting enteropathogens in suspected rotavirus vaccine-derived gastroenteritis cases. ispartof: VACCINE vol:40 issue:35 pages:5114-5125 ispartof: location:Netherlands status: published |
Databáze: | OpenAIRE |
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