Single Dose&amp;nbsp;Administration,&amp;nbsp;And&amp;nbsp;The&amp;nbsp;Influence Of&amp;nbsp;The&amp;nbsp;Timing Of&amp;nbsp;The&amp;nbsp;Booster Dose&amp;nbsp;On Immunogenicity and Efficacy Of&amp;nbsp;ChAdOx1 nCoV-19&amp;nbsp;(AZD1222)&amp;nbsp;Vaccine

Madhi, Shabir A.; Weckx, Lily Yin; Aley, Parvinder K.; Angus, Brian; Bhorat, Qasim; Cutland, Clare; Duncan, Christopher; Emary, Katherine R. W.; Ewer, Katie; Feng, Luzhao; Finn, Adam; Green, Catherine; Green, Christopher; Greenland, Melanie; Marchevsky, Natalie; Marshall, Richard P.; Mendes, Ana Verena Almeida; Minassian, Angela M.; McGregor, Alastair; Farooq, Yama G; Phillips, Daniel J.; Pittella, Ana; Ramasamy, Maheshi; Robinson, Hannah; Snape, Matthew D.; Sprinz, Eduardo; Thomson, Emma C.; Török, M. Estée; Vekemans, Johan; White, Thomas; Hill, Adrian V. S.; Lambe, Teresa

doi:10.2139/ssrn.3777268

Cited by 36 publications

(53 citation statements)

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“…An analysis by duration of interval between doses suggested that a longer duration provided increased protection 27. The efficacy of a single dose was estimated at 76% with follow-up for up to 90 days in all age groups, which is in line with our findings 27…”

Section: Discussionsupporting

confidence: 90%

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Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

Bernal

Andrews

Gower

et al. 2021

BMJ

1,000

635

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Objective To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. Design Test negative case-control study. Setting Community testing for covid-19 in England. Participants 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. Interventions Vaccination with BNT162b2 or ChAdOx1-S. Main outcome measures Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. Results Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. Conclusion Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

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Section: Discussionsupporting

confidence: 90%

“…Our results and those seen in the phase III clinical trials show similarities 4527. As in the trial of BNT162b2, we saw a decline in the odds of a positive test result among vaccinees from 10 to 13 days after the first dose.…”

Section: Discussionsupporting

confidence: 78%

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

Bernal

Andrews

Gower

et al. 2021

BMJ

1,000

635

View full text Add to dashboard Cite

show abstract

“…The S: E484K independently emerged in multiple lineages in distant geographical locations including the B.1.351 and the P.1 and those lineages showed some reduction in neutralization by sera collected from immunized individuals as well as decreased susceptibility to certain therapeutic monoclonal antibodies. Additionally, the B.1.351 and P.1 were associated with reductions in the vaccine efficacy data in locations of its predominance (23,24). The S: E484K is also present in some strains of lineage B.1.526, a lineage which was significantly associated with positives after vaccination in our cohort, even though in a previous study, it was not reported to associate with positives after vaccination (25).…”

Section: Discussionmentioning

confidence: 51%

SARS-CoV-2 Infections in mRNA Vaccinated Individuals are Biased for Viruses Encoding Spike E484K and Associated with Reduced Infectious Virus Loads that Correlate with Respiratory Antiviral IgG levels

Mostafa¹,

Luo²,

Morris

et al. 2021

Preprint

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Introduction COVID-19 large scale immunization in the US has been associated with infrequent breakthrough positive molecular testing. Whether a positive test is associated with a high viral RNA load, specific viral variant, recovery of infectious virus, or symptomatic infection is largely not known. Methods In this study, we identified 133 SARS-CoV-2 positive patients who had received two doses of either Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccines, the 2nd of which was received between January and April of 2021. The positive samples were collected between January and May of 2021 with a time that extended from 2 to 100 days after the second dose. Samples were sequenced to characterize the whole genome and Spike protein changes and cycle thresholds that reflect viral loads were determined using a single molecular assay. Local SARS-CoV-2 IgG antibodies were examined using ELISA and specimens were grown on cell culture to assess the recovery of infectious virus as compared to a control unvaccinated cohort from a matched time frame. Results Of 133 specimens, 24 failed sequencing and yielded a negative or very low viral load on the repeat PCR. Of 109 specimens that were used for further genome analysis, 68 (62.4%) were from symptomatic infections, 11 (10.1%) were admitted for COVID-19, and 2 (1.8%) required ICU admission with no associated mortality. The predominant virus variant was the alpha (B.1.1.7), however a significant association between lineage B.1.526 and amino acid change S: E484K with positives after vaccination was noted when genomes were compared to a large control cohort from a matched time frame. A significant reduction of the recovery of infectious virus on cell culture as well as delayed time to the first appearance of cytopathic effect was accompanied by an increase in local IgG levels in respiratory samples of vaccinated individuals but upper respiratory tract IgG levels were not different between symptomatic or asymptomatic infections. Conclusions Vaccination reduces the recovery of infectious virus in breakthrough infections accompanied by an increase in upper respiratory tract local immune responses.

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“…Since then, the international scientific community has mobilized to produce vaccines in an unprecedented effort to slow viral transmission and prevent severe disease and death [1]. Pooled interim analysis of four clinical trials investigating the efficacy of the Oxford-AstraZeneca's adenovirus-based vaccine ChAdOx1 nCoV-19 (AZD1222) demonstrated 70.4% efficacy in mitigating symptomatic Covid-19 after the administration of two doses [2]. Controlled trials of the Pfizer-BioNTech mRNA vaccine (BNT162b1) demonstrated 95.0% efficacy in preventing symptomatic SARS-CoV-2 infection at least 7 days post second dose [3].…”

Section: Case Reportmentioning

confidence: 99%

Heterologous immunization with Covishield and Pfizer vaccines against SARS-CoV-2 elicits a robust humoral immune response

Ostadgavahi

Booth

Sisson

et al. 2021

J Infect Dev Ctries

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Understanding the efficacy and durability of heterologous immunization schedules against SARS-CoV-2 is critical, as supply demands and vaccine choices become significant issues in the global vaccination strategy. Here we characterize the neutralizing antibodies produced in two subjects who received combination immunizations against SARS-CoV-2, first with Covishield (Oxford–AstraZeneca) vaccine, followed 33 days later with a second dose (booster) shot of the Pfizer-BioNTech vaccine. Serum samples were collected 25 days following the primary vaccination and 13 days after the secondary Pfizer vaccination. Both subjects exhibited increased levels of isotype IgG and IgM antibodies directed against the entire spike protein following immunizations. These antibodies also exhibited increased reactivity with the receptor binding domain (RBD) in the spike protein and neutralized the infectivity of replicating vesicular stomatitis virus (VSV) that contains the COVID-19 coronavirus S protein gene in place of its normal G glycoprotein. This VSV pseudovirus also contains the reporter gene for enhanced green fluorescent protein (eGFP). Antibody titers against the spike protein and serum neutralization titers against the reporter virus are reported for the 2 heterologous vaccinated individuals and compared to a positive control derived from a convalescent patient and a negative control from an unexposed individual. The Pfizer-BioNTech vaccine increased antibody binding to the spike protein and RBD, and approached levels found in the convalescent positive control. Neutralizing antibodies against the VSV-S pseudovirus in the 2 subjects also approached levels in the convalescent sera. These results firmly validate the value of the Pfizer-BioNTech vaccine in boosting immunity following initial Covishield inoculation.

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Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine

Cited by 36 publications

References 0 publications

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

SARS-CoV-2 Infections in mRNA Vaccinated Individuals are Biased for Viruses Encoding Spike E484K and Associated with Reduced Infectious Virus Loads that Correlate with Respiratory Antiviral IgG levels

Heterologous immunization with Covishield and Pfizer vaccines against SARS-CoV-2 elicits a robust humoral immune response

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