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EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334389


Third dose COVID-19 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable elderly people who exhibit suboptimal responses after primary series vaccination. We studied spike-specific immune responses in 341 staff and residents in long-term care facilities (LTCF) who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third dose vaccination strongly increased antibody responses with preferential enhancement in older people and was required to elicit neutralisation of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titres fell 21-78% within 100 days post vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a 3rd vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323027


Background: Residents of long-term care facilities (LTCF) have experienced high mortality rates from SARS-CoV-2 infection and as such have been prioritized for Covid-19 vaccination. Several countries have implemented an extended interval of up to 12 weeks between first and second vaccine doses to increase population coverage after single administration. Methods: Spike-specific immune responses that were induced following single administration of BNT162b2 or ChAdOx1 were studied in 89 staff and 35 residents within LTCFs. Quantitative antibody and cellular responses were determined as well as antibody inhibition of spike protein-ACE2 binding from viral variants. Results: 20% of staff and 34% of residents were found to have serological evidence of prior SARS-CoV-2 infection and all of these donors demonstrated strong antibody responses that were independent of age. Antibody responses were detectable within 99% and 79% of ‘infection-naive’ staff and residents respectively but were 8.2-fold lower within residents. This effect resulted from slower kinetics of antibody generation within residents which reached levels comparable to staff after only 42 days. In contrast spike-specific cellular responses were equivalent between both groups. Antibody inhibition activity against the B.1.351 and P.1 viral variants of concern was low using serum from ‘infection-naive’ older donors. Prior history of natural infection thus has a marked impact on the magnitude and quality of antibody response after a single Covid-19 vaccine in care home residents. Interpretation: Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and might be considered for an early second vaccine where possible. Funding: UK Government Department of Health and Social CareDeclaration of Interests: LS reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health.Ethics Approval Statement: Ethical approval for this study was obtained from the South Central - Hampshire B Research Ethics Committee, REC Ref: 20/SC/023.

SSRN; 2021.
Preprint in English | SSRN | ID: ppcovidwho-297180


Background: Age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for this group but there is concern that immune responses may be impaired due to immune senescence and co-morbidity. Methods: We studied antibody and cellular immune responses following COVID-19 vaccination in 202 staff and 286 residents of long-term care facilities (LTCF). Due to the high prevalence of previous infection within this environment 50% and 51% of these two groups respectively had serological evidence of prior natural SARS-CoV-2 infection. Results: In both staff and residents with previous infection the antibody responses following dual vaccination were strong and equivalent across the age course. In contrast, within infection-naïve donors these responses were reduced by 2.4-fold and 8.1-fold respectively such that values within the resident population were 2.6-fold lower than in staff. Impaired neutralisation of delta variant spike binding was also apparent within donors without prior infection. Spike-specific T cell responses were also markedly enhanced by prior infection and within infection-naive donors were 52% lower within residents compared to staff. Post-vaccine spike-specific CD4+ T cell responses displayed single or dual production of IFN-γ+ and IL-2+ whilst previous infection primed for an extended functional profile with TNF-ɑ+ and CXCL10 production. Interpretation: These data reveal suboptimal post-vaccine immune responses within infection-naïve elderly residents of LTCF and indicate the need for further optimization of immune protection through the use of booster vaccination.