Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine

Sadoff, Jerald C.; Gars, Mathieu Le; Shukarev, Georgi; Heerwegh, Dirk; Truyers, Carla; Groot, Anne Marit de; Stoop, Jeroen N.; Tete, Sarah M.; Damme, Wim Van; Leroux-Roels, Isabel; Berghmans, Pieter-Jan; Kimmel, Murray; Damme, Pierre Van; Hoon, Jan de; Smith, William M.; Stephenson, Kathryn E.; Rosa, Stephen C. De; Cohen, Kristen W.; McElrath, M. Juliana; Cormier, Emmanuel; Scheper, Gert C.; Barouch, Dan H.; Hendriks, Jenny; Struyf, Frank; Douoguih, Macaya; Hoof, Johan Van; Schuitemaker, Hanneke

doi:10.1056/nejmoa2034201

Cited by 1,063 publications

(1,085 citation statements)

References 16 publications

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“…6 Here, we report additional S-ELISA binding antibody data from these studies ( Fig. S1), in an assay homologous to the one utilized for human immunogenicity assessment, 9 to support the current correlate analysis. The estimated mean probability of protection against detectable viral load (sub-genomic mRNA (sgRNA)), together with a 95% confidence interval (CI), as a function of the level of different immune responses, was obtained using logistic regression, similarly as previously used for anthrax 10 and Ebola virus disease 11 vaccines (see statistical methods for more details).…”

Section: Sars-cov-2 Spike (S) Protein Immunogenicity As Assessed By Psupporting

confidence: 62%

SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

Roozendaal

Solforosi

Stieh

et al. 2021

Preprint

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The first COVID-19 vaccines have recently gained authorization for emergency use.1,2 At this moment, limited knowledge on duration of immunity and efficacy of these vaccines is available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short lived,3,4 and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection.5 Here we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike (S) protein in rhesus macaques6,7,8 and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We find that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of S-binding and neutralizing antibodies. These results suggest that Ad26.COV2.S could confer durable protection in humans and that immunological correlates of protection may enable the prediction of durability of protection.

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Section: Sars-cov-2 Spike (S) Protein Immunogenicity As Assessed By Psupporting

confidence: 62%

SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

Roozendaal

Solforosi

Stieh

et al. 2021

Preprint

Self Cite

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“…[accessed 9 February 2021]) indicate 66% efficacy across a range of countries where novel SARS-CoV-2 variants are emerging, such as in South Africa (see Figure 1, Table 1 and Section 5 below). Recently published Phase II data [31] and interim Phase III data provide evidence for acceptable safety, tolerability and immunogenicity (Tables 2 and 3).…”

Section: Viral Vector-based (Non-replicating) Vaccines-safety/reactogmentioning

confidence: 95%

“…Four groups (Astra Zeneca/University of Oxford (AZ/Ox), CanSino Biologics, Gamaleya Research Institute and Johnson & Johnson/Janssen (J&J)) have all adopted the use of non-replicating adenoviral vectors to drive the expression of the full-length SARS-CoV-2 spike glycoprotein (5 × 10 10 or 10 11 viral particles for each dose injection) to induce an immune response [18,19,[25][26][27][28][29][30][31]. The differences between them lie in the chosen vector strain and immunization schedules.…”

Section: Viral Vector-based (Non-replicating) Vaccinesmentioning

confidence: 99%

“…AZ/Ox (vaccine named AZ1222 or Covishield in India) (https://www.bbc.com/news/world-asia-india-55748124 [accessed 9 February 2021]) uses an adenoviral vector that infects chimpanzees but not humans [25,26]. CanSino (Ad5-nCoV) uses a recombinant version of Ad5 ad-enovirus that naturally transmits in humans [28,29], while J&J (Ad26.COV2.S) uses a variant adenovirus Ad26 that is not normally (or only rarely) encountered by the human population [31]. Gamaleya (Sputnik V) uses a combination prime with Ad26 and boost with Ad5 [19,30].…”

Section: Viral Vector-based (Non-replicating) Vaccinesmentioning

confidence: 99%

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Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective

Funk

Laferrière²,

Ardakani³

2021

Viruses

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The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral damage to societies and economies, and has destabilized mental health and well-being. Early in 2020, unprecedented efforts went into the development of vaccines that generate effective antibodies to the SARS-CoV-2 virus. Teams developing twelve candidate vaccines, based on four platforms (messenger RNA, non-replicating viral vector, protein/virus-like particle, and inactivated virus) had initiated or announced the Phase III clinical trial stage by early November 2020, with several having received emergency use authorization in less than a year. Vaccine rollout has proceeded around the globe. Previously, we and others had proposed a target product profile (TPP) for ideal/optimal and acceptable/minimal COVID-19 vaccines. How well do these candidate vaccines stack up to a harmonized TPP? Here, we perform a comparative analysis in several categories of these candidate vaccines based on the latest available trial data and highlight the early successes as well as the hurdles and barriers yet to be overcome for ending the global COVID-19 pandemic.

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“…Recent phase 3 trials have led to the approval of two COVID-19 vaccines in the United States, and other vaccines have been approved in other countries or show promise for approval in the near future (7,8). This study provides strong further evidence supporting the use of vaccination to prevent and reduce the severity of COVID-19.…”

Section: Discussionmentioning

confidence: 60%

FDA-approved COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system

Soundararajan

Pawlowski

Lenehan

et al. 2021

Preprint

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Large Phase 3 clinical trials of the two FDA-approved COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,598 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,299 individuals receiving at least one dose of either vaccine with 31,299 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. Administration of two COVID-19 vaccine doses was 89.0% effective in preventing SARS-CoV-2 infection (95% CI: 69.1-97.2%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.

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Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine

Cited by 1,063 publications

References 16 publications

SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective

FDA-approved COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system

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