Real-world effectiveness of Ad26.COV2.S adenoviral vector vaccine for COVID-19

Corchado-Garcia, Juan; Zemmour, David; Hughes, Travis S.; Cristea-Platon, Tudor; Lenehan, Patrick; Pawlowski, Colin; Bade, Sairam; O’Horo, John C.; Gores, Gregory J.; Williams, Amy W.; Badley, Andrew D.; Halamka, John; Virk, Abinash; Swift, Melanie D.; Wagner, Tyler; Soundararajan, Venky

doi:10.1101/2021.04.27.21256193

Cited by 28 publications

(13 citation statements)

References 11 publications

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“…The continual emergence of SARS-CoV-2 variants with increased transmissibility and capacity for immune escape, such as B.1.1.7 ("UK variant") and P.1 ("Brazilian variant"), threatens to prolong the pandemic through devastating outbreaks such as the one currently being witnessed in India 2 . While multiple vaccines have demonstrated high effectiveness in clinical trials and real world studies [3][4][5] , there have been reports of "vaccine breakthrough infections" with SARS-CoV-2 variants 6,7 . A recent study described two such cases in New York, at least one of which occurred despite confirmation of a robust neutralizing antibody response.…”

Section: Introductionmentioning

confidence: 99%

Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections

Venkatakrishnan

Lenehan

Ghosh

et al. 2021

Preprint

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The raging COVID-19 pandemic in India and reports of “vaccine breakthrough infections” globally have raised alarm mandating the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed over 1.3 million SARS-CoV-2 genomes from 178 countries and performed whole-genome viral sequencing from 53 COVID-19 patients, including 20 vaccine breakthrough infections. We identified 116 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a three-month window. Deletions in the Spike protein N-terminal domain (NTD) are highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 18.2, 95% CI: 7.53-48.7; p=1.465x10-18). In the recent COVID-19 surge in India, an NTD deletion (ΔF157/R158) increased over 10-fold in prevalence from February 2021 (1.1%) to April 2021 (15%). During the recent surge in Chile, an NTD deletion (Δ246-253) increased rapidly over 30-fold in prevalence from January 2021 (0.86%) to April 2021 (33%). Strikingly, these simultaneously emerging deletions associated with surges in different parts of the world both occur at an antigenic supersite that is targeted by neutralizing antibodies. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences and identified deletions within this NTD antigenic supersite in a patient with vaccine breakthrough infection (Δ156-164) and other deletions from unvaccinated severe COVID-19 patients that could represent emerging deletion-prone regions. Overall, the expanding repertoire of Spike protein deletions throughout the pandemic and their association with case surges and vaccine breakthrough infections point to antigenic minimalism as an emerging evolutionary strategy for SARS-CoV-2 to evade immune responses. This study highlights the urgent need to sequence SARS-CoV-2 genomes at a larger scale globally and to mandate a public health policy for transparent reporting of relevant clinical annotations (e.g. vaccination status) in order to aid the development of comprehensive therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections

Venkatakrishnan

Lenehan

Ghosh

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Two studies reported efficacy and effectiveness estimates for the single dose Johnson & Johnson vaccine which informed 5 of the 12 possible estimates 54,55 (Figure 5 and Table 2). We estimated a 66%, 73%, 83%, efficacy for wild-type against any infection, symptomatic disease, and severe disease respectively.…”

Section: Johnson and Johnson (Viral Vector)mentioning

confidence: 99%

“…We estimated a 66%, 73%, 83%, efficacy for wild-type against any infection, symptomatic disease, and severe disease respectively. Five estimates for efficacy against symptomatic disease were identified ranging from 66.9% (95% CI: 59.0, 73.4) 54 to 76.7% (95% CI: 30.3, 95.3) 55 . No data were available for efficacy against transmission, therefore we assumed this to be the same as for AstraZeneca.…”

Section: Johnson and Johnson (Viral Vector)mentioning

confidence: 99%

Interpreting estimates of coronavirus disease 2019 (COVID-19) vaccine efficacy and effectiveness to inform simulation studies of vaccine impact: a systematic review

et al. 2021

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Background: The multiple efficacious vaccines authorised for emergency use worldwide represent the first preventative intervention against coronavirus disease 2019 (COVID-19) that does not rely on social distancing measures. The speed at which data are emerging and the heterogeneities in study design, target populations, and implementation make it challenging to interpret and assess the likely impact of vaccine campaigns on local epidemics. We reviewed available vaccine efficacy and effectiveness studies to generate working estimates that can be used to parameterise simulation studies of vaccine impact. Methods: We searched MEDLINE, the World Health Organization’s Institutional Repository for Information Sharing, medRxiv, and vaccine manufacturer websites for studies that evaluated the emerging data on COVID-19 vaccine efficacy and effectiveness. Studies providing an estimate of the efficacy or effectiveness of a COVID-19 vaccine using disaggregated data against SARS-CoV-2 infection, symptomatic disease, severe disease, death, or transmission were included. We extracted information on study population, variants of concern (VOC), vaccine platform, dose schedule, study endpoints, and measures of impact. We applied an evidence synthesis approach to capture a range of plausible and consistent parameters for vaccine efficacy and effectiveness that can be used to inform and explore a variety of vaccination strategies as the COVID-19 pandemic evolves. Results: Of the 602 articles and reports identified, 53 were included in the analysis. The availability of vaccine efficacy and effectiveness estimates varied by vaccine and were limited for VOCs. Estimates for non-primary endpoints such as effectiveness against infection and onward transmission were sparse. Synthesised estimates were relatively consistent for the same vaccine platform for wild-type, but was more variable for VOCs. Conclusions: Assessment of efficacy and effectiveness of COVID-19 vaccines is complex. Simulation studies must acknowledge and capture the uncertainty in vaccine effectiveness to robustly explore and inform vaccination policies and policy around the lifting of non-pharmaceutical interventions.

show abstract

Section: Introductionmentioning

confidence: 99%

Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections

Venkatakrishnan

Lenehan

Ghosh

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

The raging COVID-19 pandemic in India and reports of vaccine breakthrough infections globally have raised alarm mandating the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed over 1.3 million SARS-CoV-2 genomes from 178 countries and performed whole-genome viral sequencing from 53 COVID-19 patients, including 20 vaccine breakthrough infections. We identified 116 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a three-month window. Deletions in the Spike protein N-terminal domain (NTD) are highly enriched for these surge-associated mutations (Odds Ratio = 18.2, 95% CI: 7.53-48.7; p=1.465x10-18). In the recent COVID-19 surge in India, an NTD deletion (ΔF157/R158) increased over 10-fold in prevalence from February 2021 (1.1%) to April 2021 (15%). During the recent surge in Chile, an NTD deletion (Δ246-253) increased rapidly over 30-fold in prevalence from January 2021 (0.86%) to April 2021 (33%). Strikingly, these simultaneously emerging deletions associated with surges in different parts of the world both occur at an antigenic supersite that is targeted by neutralizing antibodies. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences and identified deletions within this NTD antigenic supersite in a patient with vaccine breakthrough infection (Δ156-164) and other deletions from unvaccinated severe COVID-19 patients that could represent emerging deletion-prone regions. Overall, the expanding repertoire of NTD deletions throughout the pandemic and their association with case surges and vaccine breakthrough infections point to antigenic minimalism as an emerging evolutionary strategy for SARS-CoV-2 to evade immune responses. This study highlights the urgent need to sequence viral genomes at a larger scale globally and to mandate that sequences are deposited with more granular and transparent clinical annotations to ensure that therapeutic development keeps pace with the evolution of SARS-CoV-2.

show abstract

Real-world effectiveness of Ad26.COV2.S adenoviral vector vaccine for COVID-19

Cited by 28 publications

References 11 publications

Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections

Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections

Interpreting estimates of coronavirus disease 2019 (COVID-19) vaccine efficacy and effectiveness to inform simulation studies of vaccine impact: a systematic review

Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections

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