Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England

Amirthalingam, Gayatri; Bernal, Jamie Lopez; Andrews, Nick; Whitaker, Heather; Gower, Charlotte; Stowe, Julia; Tessier, Elise; Subbarao, Sathyavani; Ireland, Georgina; Baawuah, Frances; Linley, Ezra; Warrener, Lenesha; O’Brien, Michelle; Whillock, Corinne; Moss, Paul; Ladhani, Shamez; Brown, Kevin E.; Ramsay, Mary

doi:10.1038/s41467-021-27410-5

Cited by 91 publications

(104 citation statements)

References 25 publications

(17 reference statements)

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“…Our followup study confirms that binding and neutralizing antibody activities induced by COVID-19 mRNA vaccines are significantly weaker in older adults at all time points following a twodose immunization series. In multivariable analyses, a higher number of chronic health conditions was also consistently independently associated with a weaker binding antibody response after two COVID-19 vaccine doses, while a longer interval between first and second vaccine doses was consistently Page 13 of 32 associated with higher binding antibody responses, as previously reported [34][35][36] . We also showed that binding antibody responses decline more rapidly over time in older adults, which can be attributed to a higher number of chronic health conditions in this group.…”

Section: Discussionsupporting

confidence: 76%

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Mwimanzi

Lapointe

Cheung

et al. 2022

Preprint

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Background. Two-dose mRNA vaccines reduce COVID-19 related hospitalization and mortality, but immune protection declines over time. As such, third vaccine doses are now recommended, particularly for older adults. We examined immune response durability up to 6 months after two vaccine doses, and immunogenicity after a third vaccine dose, in 151 adults ranging in age from 24 to 98 years. Methods. Specimens were collected from 81 healthcare workers (median age 41 years), 56 older adults (median 78 years) and 14 COVID-19 convalescent individuals (median 48 years), at one, three and six months following the second dose, and from 15 HCW, 28 older adults and 3 convalescent individuals at one month following a third dose. Binding antibodies to the SARS-CoV-2 spike receptor binding domain were quantified using a commercial immunoassay. Virus neutralizing activity was assessed using a live SARS-CoV-2 infection assay. Results. Compared to healthcare workers, older adults displayed ~0.3 log10 lower peak binding antibodies one month after the second dose (p<0.0001) and modestly faster rates of antibody decline thereafter (p=0.0067). A higher burden of chronic health conditions was independently associated with faster rates of antibody decline after correction for age, sociodemographic factors, and vaccine-related variables. Peak neutralizing activity was 4-fold lower in older adults one month after the second dose (p<0.0001) and became undetectable in the majority of individuals by six months. One month after a third dose, binding antibodies and neutralizing activities surpassed peak values achieved after two doses in both healthcare workers and older adults, and differences between these groups were no longer statistically significant. Compared to both naive groups, convalescent individuals displayed slower rates of binding antibody decline (p<0.006) and maintained higher neutralizing activity six months after the second dose. Conclusions. Immune responses to two-dose COVID-19 mRNA vaccines are overall weaker in older adults, and also decline more quickly over time, compared to younger adults. A third COVID-19 mRNA vaccine dose enhanced binding and neutralizing antibodies to levels higher than those observed after two vaccine doses, but the rate of decline of these responses should be monitored, particularly in older adults with a higher burden of chronic health conditions.

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Section: Discussionsupporting

confidence: 76%

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Mwimanzi

Lapointe

Cheung

et al. 2022

Preprint

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“… 19 In the United Kingdom, a 2-dose program with a 12-wk gap between doses, predominantly with ChAdOx1-S or BNT162b2 vaccines, was reported as showing 79% reduction in risk of infection during the Alpha-dominant and 67% risk reduction during the Delta variant–dominant periods, 28 with the extended dosing schedule associated with superior VE. 25 Lopez Bernal et al 29 reported a modest reduction in VE against the Delta variant in a test-negative, case–control study in the general UK population. Direct comparisons of VE between different studies are challenging since VE wanes with time and at variable rates in different populations, and therefore, follow-up period and demographic characteristics must be considered.…”

Section: Discussionmentioning

confidence: 99%

“…National policy mandated a 10- to 12-wk gap between first and second vaccine doses, irrespective of vaccine type. 24 , 25 …”

Section: Methodsmentioning

confidence: 99%

Real-world Effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S Vaccines Against SARS-CoV-2 in Solid Organ and Islet Transplant Recipients

et al. 2022

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Background. The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. Methods. We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals. Case fatality rate ratios were adjusted using a Cox proportional hazards model to generate hazard ratio (95% confidence interval). Results. On August 31, 2021, it was found that 3080 (7.1%) were unvaccinated, 1141 (2.6%) had 1 vaccine dose, and 39 260 (90.3%) had 2 vaccine doses. There were 4147 SARS-CoV-2 infections and 407 deaths (unadjusted case fatality rate 9.8%). The riskadjusted infection incidence rate ratio was 1.29 (1.03-1.61), implying that vaccination was not associated with reduction in risk of testing positive for SARS-CoV-2 RNA. Overall, the hazard ratio for death within 28 d of SARS-CoV-2 infection was 0.80 (0.63-1.00), a 20% reduction in risk of death in vaccinated patients (P = 0.05). Two doses of ChAdOx1-S were associated with a significantly reduced risk of death (hazard ratio, 0.69; 0.52-0.92), whereas vaccination with BNT162b2 was not (0.97; 0.71-1.31). Conclusions. Vaccination of SOT recipients confers some protection against SARS-CoV-2-related mortality, but this protection is inferior to that achieved in the general population. SOT recipients require additional protective measures, including further vaccine doses, antiviral drugs, and nonpharmaceutical interventions. (Transplantation 2022;106: 436-446).

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“…Existing evidence suggests that vaccine effectiveness increases with longer intervals between doses and, if this also applies to third doses, the administration interval will also need to be considered. 25 At the same time, it is possible that third doses will be more reactogenic than previous doses, especially if the recipient receives different vaccines for the initial and booster doses. 26 Attractive alternatives include half-dose boosters or boosting with variant-targeted vaccines, which are both under investigation.…”

Section: Discussionmentioning

confidence: 99%

“…For the United Kingdom and countries with administration intervals that are longer than the licensed interval, another important consideration is that the extended interval of 8 to 12 weeks between vaccine doses provides higher serologic responses and increased vaccine effectiveness than the licensed interval of 3 to 4 weeks for mRNA vaccines, 25 which may provide the populations in these countries with better, longer-term protection. 12 This hypothesis is supported by our current findings comparing short and long administration intervals among persons 80 years of age or older.…”

Section: Discussionmentioning

confidence: 99%

Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines

Andrews

Tessier²,

Stowe³

et al. 2022

N Engl J Med

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561

508

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Background Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. Methods We used a test-negative case–control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. Results Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. Conclusions We observed limited waning in vaccine effectiveness against Covid-19–related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

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Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England

Cited by 91 publications

References 25 publications

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Real-world Effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S Vaccines Against SARS-CoV-2 in Solid Organ and Islet Transplant Recipients

Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines

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