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Nat Microbiol ; 7(8): 1180-1188, 2022 08.
Article in English | MEDLINE | ID: covidwho-1931412


SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70-89 years, vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , Membrane Glycoproteins/chemistry , Neutralization Tests , SARS-CoV-2/genetics , Viral Envelope Proteins/chemistry
Euro Surveill ; 26(5)2021 02.
Article in English | MEDLINE | ID: covidwho-1067625


Two London care homes experienced a second COVID-19 outbreak, with 29/209 (13.9%) SARS-CoV-2 RT-PCR-positive cases (16/103 residents, 13/106 staff). In those with prior SARS-CoV-2 exposure, 1/88 (1.1%) individuals (antibody positive: 87; RT-PCR-positive: 1) became PCR-positive compared with 22/73 (30.1%) with confirmed seronegative status. After four months protection offered by prior infection against re-infection was 96.2% (95% confidence interval (CI): 72.7-99.5%) using risk ratios from comparison of proportions and 96.1% (95% CI: 78.8-99.3%) using a penalised logistic regression model.

Antibodies, Viral/blood , COVID-19/prevention & control , Disease Outbreaks/prevention & control , Nursing Homes/statistics & numerical data , Reinfection/prevention & control , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/immunology , COVID-19 Serological Testing , Female , Humans , London , Male , Middle Aged , Pandemics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Whole Genome Sequencing