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Cited by 629SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesAnimal Virus Infections Studies

Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant

Open access
Shinde, Vivek, Bhikha, Sutika, Hoosain, Zaheer, Archary, Moherndran, Bhorat, Qasim, Fairlie, Lee, Lalloo, Umesh, Masilela, Mduduzi S.L. +41 more·2021·New England Journal of Medicine
DOI 10.1056/nejmoa2103055PMC PMC8091623

Published version of a preprint

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Abstract

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission. METHODS: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection. RESULTS: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups. CONCLUSIONS: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).

AI snapshot

Written from the paper’s full text.

TL;DR

In a South African phase 2a/b trial during predominant B.1.351 circulation, two doses of NVX-CoV2373 had 49.4% efficacy against symptomatic Covid-19 in baseline seronegative participants and 60.1% in HIV-negative participants. Post-hoc efficacy against B.1.351 was 51.0% in HIV-negative participants, with mostly mild-to-moderate disease and acceptable preliminary safety.

Key findings

  • Among 2684 baseline seronegative participants, 15 Covid-19 cases occurred in NVX-CoV2373 recipients versus 29 in placebo recipients, giving vaccine efficacy of 49.4% (95% CI, 6.1 to 72.8).
  • In HIV-negative baseline seronegative participants, vaccine efficacy was 60.1% (95% CI, 19.9 to 80.1); post-hoc efficacy against B.1.351 was 51.0% (95% CI, −0.6 to 76.2) in HIV-negative participants and 43.0% (95% CI, −9.8 to 70.4) in the combined HIV-negative and PLWH population.
  • Of 41 sequenced primary efficacy endpoint cases, 38 (92.7%) were the B.1.351 variant.
  • Solicited local and systemic adverse events were predominantly mild to moderate and transient, and more common with NVX-CoV2373; serious adverse events were rare (2 vs. 1) and none were assessed as related to trial vaccine.

Methods

  • Phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa; participants were healthy HIV-negative adults 18 to 84 years or medically stable PLWH 18 to 64 years, randomized 1:1 to two doses 21 days apart of NVX-CoV2373 (5 μg recombinant spike protein with 50 μg Matrix-M1 adjuvant) or saline placebo.
  • Primary endpoints were safety and vaccine efficacy ≥7 days after the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants; the per-protocol efficacy set included baseline seronegative participants, and vaccine efficacy was estimated with Poisson regression with robust error variance.
  • A total of 4387 participants were randomized and dosed at least once (2199 NVX-CoV2373, 2188 placebo), 4332 received both injections, and 2684 baseline seronegative participants were evaluable for the primary efficacy analysis; approximately 30% were seropositive at baseline, and 94% of the efficacy population was HIV-negative and 6% PLWH.

Limitations

  • Stated: efficacy results are preliminary (median follow-up of 66 and 45 days after first and second doses), limited to the primary endpoint and subgroups plus post-hoc B.1.351 sequencing, and caution is warranted for the small PLWH cohort; the study captured almost exclusively mild to moderate Covid-19 in a predominantly young, healthy population, so efficacy against severe Covid-19 could not be reported.
  • Stated/evident: the number of endpoint cases was small, and confidence intervals were wide, including for post-hoc B.1.351 efficacy estimates that crossed zero; the study was not powered to detect efficacy in PLWH.
  • Evident: safety reporting was preliminary and based on Stage 1 participants only (first 889 HIV-negative and first 80 PLWH participants with at least Day 35 follow-up), limiting broader safety conclusions at the time of analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1056/nejmoa2103055

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Approximately 30% of participants were seropositive at baseline by anti-S IgG antibodies.

    “Approximately 30% of participants were seropositive at baseline.”
    • Also stated in: § Participants · plain
      “Approximately 30% of participants were seropositive at baseline by anti-S IgG antibodies (sensitivity 94.7% and specificity 96.4% at a predefined anti-S IgG threshold; see Supplementary Appendix).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The primary phase 2b efficacy endpoint success criterion was met.

    “thereby meeting the primary phase 2b efficacy endpoint success criterion”
    Quote in the paperSubstantial claim
  • Findingown data

    The preliminary incidence of Covid-19 in baseline seronegative placebo participants was comparable to that in baseline seropositive placebo participants during the initial 60 days of follow-up.

    “was comparable to the incidence in baseline seropositive placebo participants”
    Quote in the paperNot a substantial claim
  • Findingown data

    The post-hoc NVX-CoV2373 vaccine efficacy against the B.1.351 variant in the combined HIV-negative and PLWH population was 43.0% (95% CI, −9.8 to 70.4).

    “and 43.0% (95% CI: −9.8 to 70.4) in the combined HIV-negative and PLWH population (14 cases in NVX-CoV2373 and 24 in placebo recipients).”
    Quote in the paperSubstantial claim
  • Findingown data

    During the initial 60 days of follow-up, the preliminary incidence of Covid-19 in baseline seropositive placebo participants was 5.2% (95% CI, 3.6 to 7.2).

    “was comparable to the incidence in baseline seropositive placebo participants (5.2% [95% CI: 3.6 to 7.2]; 14 mild and 21 moderate cases out of 674 participants)”
    Quote in the paperNot a substantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 14

  • May combine two claims.

    Findingown data

    Solicited local and systemic adverse events were predominantly mild to moderate and transient, and more common in NVX-CoV2373 recipients.

    “Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX-CoV2373”
    • Also stated in: § Safety · plain
      “Briefly, solicited local and systemic adverse events were predominantly mild to moderate and transient, and more common in NVX-CoV2373 recipients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Medically attended adverse events and serious adverse events were infrequent but occurred more often in the NVX-CoV2373 group versus placebo (13 vs 6, and 2 vs 1, respectively).

    “Medically attended adverse events (Table S10) and serious adverse events (Table S11) were infrequent but occurred more often in the NVX-CoV2373 group versus placebo (13 vs 6, and 2 vs 1, respectively)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Severe local adverse events were infrequent but occurred more often in the seronegative NVX-CoV2373 group after the second dose (4%) versus placebo (1%).

    “Severe local adverse events were infrequent but occurred more often in the seronegative NVX-CoV2373 group after the second dose (4%) versus placebo (1%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Severe systemic adverse events increased in the seronegative NVX-CoV2373 group after the second dose (4%) but were comparable to placebo (4%).

    “Severe systemic adverse events, albeit infrequent, increased in the seronegative NVX-CoV2373 group after the second dose (4%) but were comparable to placebo (4%), particularly fatigue and headache”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The efficacy results are preliminary, with median follow-up of 66 and 45 days following first and second doses, respectively.

    “The efficacy results are preliminary (median follow-up of 66 and 45 days following first and second doses, respectively)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The B.1.351 variant emerged in the Eastern Cape Province, South Africa, in October 2020, and rapidly spread to become the dominant circulating strain throughout the country during November and December 2020.

    “The B.1.351 variant is reported to have emerged in the Eastern Cape Province, South Africa, in October 2020, and rapidly spread to become the dominant circulating strain throughout the country during November and December 2020,15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Tegally H, Wilkinson E, Giovanetti M, Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv 2020. 10.1101/2020.12.21.20248640.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The N501Y mutation is known to increase binding affinity of the spike protein to the human angiotensin-converting enzyme 2 receptor.

    “The N501Y mutation is known to increase binding affinity of the spike protein to the human angiotensin-converting enzyme 2 receptor,21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Starr TN, Greaney AJ, Hilton SK, Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 2020; 182: 1295– 131. 32841599 PMC7418704 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a phase 2 trial in South Africa (N=2026), ChAdOx1-nCoV19 reported vaccine efficacy of 22% (95% CI, −50 to 60) overall, and 10% (95% CI, −77 to 55) against the B.1.351 variant, with the latter comprising 95% of cases.

    “ChAdOx1-nCoV19 was evaluated in a phase 2 trial (N=2026) in South Africa, in a study population resembling ours with predominantly mild to moderate Covid-19, and reported vaccine efficacy of 22% (95% CI: −50 to 60) overall, and 10% (95% CI: −77 to 55) against the B.1.351 variant, with the latter comprising 95% of cases.25”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Madhi SA, Baillie V, Cutland CL. Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa. medRxiv 2021. https://www.medrxiv.org/content/10.1101/2021.02.10.21251247v1. PMC7993410 33725432 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Enrollment was staggered into Stage 1 and Stage 2, with progression requiring favorable review of safety data through Day 7 against prespecified vaccination pause rules.

    “As a safety measure, enrollment was staggered into Stage 1 (defined by the first 1/3 of targeted enrollment) and Stage 2 (the remainder of enrollment) for both HIV-negative and PLWH groups, with progression from Stage 1 to Stage 2 in each group requiring favorable review of safety data through Day 7 from the prior stage against prespecified vaccination pause rules”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The trial was randomized, observer-blinded, and placebo-controlled.

    “In this randomized, observer-blinded, placebo-controlled phase 2a/b trial, we assessed the safety and efficacy of two doses of NVX-CoV2373, administered 21 days apart.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The trial protocol was approved by the South African Health Products Regulatory Authority and Institutional Ethics Review Boards.

    “The trial protocol was approved by the South African Health Products Regulatory Authority (SAHPRA; Ref 20200420) and Institutional Ethics Review Boards”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    At the time of analysis, the study had captured almost exclusively mild to moderate Covid-19 endpoints in a predominantly young, healthy population, and therefore could not report on vaccine efficacy against severe Covid-19.

    “Importantly, at the time of analysis, the study had captured almost exclusively mild to moderate Covid-19 endpoints in a predominantly young, healthy population; consequently, we have not as yet been able to report on vaccine efficacy against severe Covid-19.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Most large Covid-19 vaccine efficacy trials have reported notably increased vaccine efficacy against severe versus mild to moderate disease.

    “Most large Covid-19 vaccine efficacy trials have reported notably increased vaccine efficacy against severe versus mild to moderate disease.4–7”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [4] Baden FP, Thomas SJ, Kitchin N,; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383: 2603– 15. 33301246 PMC7745181 source

      Not checked in the free run.

    • cites [5] Polack FP, Thomas SJ, Kitchin N,; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383: 2603– 15. 33301246 PMC7745181 source

      Not checked in the free run.

    • cites [6] Logunov DY, Dolzhikova IV, Shcheblyakov DV, Safety and efficacy of an rAd26 and rAd5 vector-based heter8ologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021. 10.1016/S0140-6736(21)00234-8. PMC7852454 33545094 source

      Not checked in the free run.

    • cites [7] Voysey M, Clemens SAC, Madhi SA, Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021; 397: 99– 111. 33306989 PMC7723445 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the interim analysis of the UK phase 3 study, relatively high levels of efficacy were observed against both the matched prototype-like, pre-variant strains (vaccine efficacy 96%) and the B.1.1.7 variant (vaccine efficacy 86%).

    “In the interim analysis of our UK phase 3 study, relatively high levels of efficacy were observed against both the matched prototype-like, pre-variant strains (vaccine efficacy 96%), and the B.1.1.7 variant (vaccine efficacy 86%).23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK phase 3 trial. Novavax, Inc. January 28, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3. Accessed February 18, 2021.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The official event-driven efficacy analysis targeted a minimum of 23 endpoints to provide approximately 90% power to detect vaccine efficacy of 80% based on an incidence rate of symptomatic Covid-19 of 2% to 6% in the placebo group.

    “The official, event-driven efficacy analysis targeted a minimum number of 23 endpoints (range of 23‒50) to provide approximately 90% power to detect vaccine efficacy of 80% based on an incidence rate of symptomatic Covid-19 of 2% to 6% in the placebo group.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Injections were administered by unblinded staff not otherwise involved with other study procedures or data collection, and all other study staff and participants remained blinded to treatment assignment.

    “administered by unblinded staff not otherwise involved with other study procedures or data collection. All other study staff and trial participants remained blinded to treatment assignment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The N501Y mutation has been reported to increase transmissibility of the B.1.17 variant circulating in the UK.

    “and has been reported to increase transmissibility of the B.1.17 variant circulating in the UK.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Volz E, Mishra S, Chand M, Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data. medRxiv 2021. https://doi.org/10.1101.2020.12.30.20249034. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The trial was registered in Clinicaltrials.gov (NCT045333990) and the Pan African Clinical trials Registry (PACTR202009726132275).

    “registered in Clinicaltrials.gov (NCT045333990 and the Pan African Clinical trials Registry (PACTR202009726132275).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    No prespecified vaccination pause rules were triggered.

    “No prespecified vaccination pause rules were triggered.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Participants were randomly assigned in a 1:1 ratio to receive NVX-CoV2373 or saline placebo.

    “Participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections, 21 days apart, of either NVX-CoV2373 (5 μg recombinant spike protein with 50 μg Matrix-M1 adjuvant) or saline placebo”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The primary efficacy analysis was carried out at an overall one-sided type I error rate of 0.025.

    “This analysis was carried out at an overall one-sided type I error rate of 0.025 for the single primary efficacy endpoint.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant.

    “The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant.”
    • Also stated in: § DISCUSSION · boosted
      “In conclusion, we have demonstrated that a prototype-sequenced NVX-CoV2373 vaccine was efficacious and induced notable cross-protection in the setting of dominant circulation of B.1.351 variants.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the South African arm (N=6576) of a large multi-national phase 3 study evaluating the efficacy of a single dose of Ad26.COV2.S, vaccine efficacy against moderate to severe Covid-19 was reported to be 52% and 64%, 14 days and 28 days post-first dose, respectively, with 95% of cases reportedly due to the B.1.351 variant.

    “In the South African arm (N=6576) of a large multi-national phase 3 study evaluating the efficacy of a single dose of Ad26.COV2.S, vaccine efficacy against moderate to severe Covid-19 was reported to be 52% and 64%, 14 days and 28 days post-first dose, respectively, with 95% of cases reportedly due to the B.1.351 variant”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] US Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee February 26, 2021 Meeting Announcement. Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-february-26-2021-meeting-announcement. Accessed March 1, 2021.

      Not checked in the free run.

    • cites [24] Johnson & Johnson announces single-shot Janssen COVID-19 vaccine candidate met primary endpoints in interim analysis of its phase 3 ENSEMBLE trial. January 29, 2021. https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial. Accessed February 18, 2021.

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The observation of comparable incidence in seropositive and seronegative placebo participants is consistent with the lack of incremental benefit conferred by pre-existing immunity in vaccine recipients, as evidenced by consistent levels of efficacy regardless of baseline serostatus.

    “This observation is consistent with the lack of incremental benefit conferred by pre-existing immunity in vaccine recipients as evidenced by consistent levels of efficacy regardless of baseline serostatus.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Baseline seropositive and seronegative placebo participants had similar risk of exposure to SARS-CoV-2 during follow-up.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Safety oversight, including for specific vaccination pause rules, was performed by an independent safety monitoring committee.

    “Safety oversight, including for specific vaccination pause rules, was performed by an independent safety monitoring committee.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The NVX-CoV2373 vaccine had an acceptable safety and reactogenicity profile.

    “Preliminary safety data continued to indicate an acceptable safety and reactogenicity profile.11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Keech C, Albert G, Cho I, Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med 2020: 383: 2320– 32. 32877576 PMC7494251 source

      Not checked in the free run.

26 of 26

  • The paper relies on this without support.

    Baseline seropositive and seronegative placebo participants had similar risk of exposure to SARS-CoV-2 during follow-up.

    “was comparable to the incidence in baseline seropositive placebo participants”
    “This report provides evidence in the setting of a controlled vaccine trial that prior infection with first-wave prototype-like, pre-B.1.351 viruses did not appear to reduce the risk of Covid-19 due to re-infection with B.1.351 variants among placebo recipients during the initial 2 months of follow-up.”
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Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Several studies have shown reduced vaccine efficacy against mild to moderate COVID-19 in countries where B.1.351 was dominant, although protection against severe disease appears preserved.

    “Several studies have now shown that there is reduced vaccine efficacy against mild to moderate disease in countries where B1.351 was dominant (Zhou et al., 2021; Shinde et al., 2021; Madhi et al., 2021, Vaccines and Related Biological Products Advisory Committee, 2021), although protection against severe disease appears to be preserved.”

    From Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (2021) · cites this paper as Shinde et al., 2021

  • Reinfections with the Beta variant occurred commonly during a phase IIb trial of the NVX-CoV2373 vaccine performed in South Africa as approximately one third of infections in both the vaccine and placebo arms were reinfections.

    “Reinfections with the Beta variant occurred commonly during a phase IIb trial of the NVX-CoV2373 vaccine performed in South Africa as approximately one third of infections in both the vaccine and placebo arms were reinfections 216 .”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [216]

  • In a phase II trial of NVX-CoV2373 in South Africa in which 38 of 41 infections were caused by the Beta variant, the estimated vaccine efficacy was 49%.

    “In a phase II trial of NVX-CoV2373 in South Africa in which 38 of 41 infections were caused by the Beta variant, the estimated vaccine efficacy was 49% 216 .”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [216]

  • NVX-CoV2373 has shown efficacy against the B.1.351 variant, though lower (51.0%) than against B.1.1.7 and non-B.1.1.7 strains.

    “the NVX-CoV2373 vaccine has also shown efficacy against the B.1.351variant, albeit at a lower level (51.0%) than has been shown for the B.1.1.7 and non-B.1.1.7 strains.”

    From Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine (2021) · cites this paper as [18]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Two efficacy estimates for the same subgroup

    Major

    Consecutive sentences report 60.1% and 52.2% vaccine efficacy for baseline-seronegative, HIV-negative participants, without identifying a different analysis or endpoint.

  • Conflicting upper age limit for participants living with HIV

    Minor

    The abstract allows medically stable participants living with HIV up to age 84, whereas the Methods section limits that subgroup to age 64.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK phase 3 trial. Press release January 28 2021 (https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3).
  2. Johnson & Johnson announces single-shot Janssen COVID-19 vaccine candidate met primary endpoints in interim analysis of its phase 3 ENSEMBLE trial. Press release January 29 2021 (https://www.janssen.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints).

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Authors
Shinde, V., Bhikha, S., Hoosain, Z., Archary, M., Bhorat, Q., Fairlie, L., Lalloo, U., Masilela, M. S. L., Moodley, D., Hanley, S., Fouche, L., Louw, C., Tameris, M., Singh, N., Goga, A., Dheda, K., Grobbelaar, C., Kruger, G., Carrim-Ganey, N., Baillie, V., de Oliveira, T., Lombard Koen, A., Lombaard, J. J., Mngqibisa, R., Bhorat, A. E., Benadé, G., Lalloo, N., Pitsi, A., Vollgraaff, P.-L., Luabeya, A., Esmail, A., Petrick, F. G., Oommen-Jose, A., Foulkes, S., Ahmed, K., Thombrayil, A., Fries, L., Cloney-Clark, S., Zhu, M., Bennett, C., Albert, G., Faust, E., Plested, J. S., Robertson, A., Neal, S., Cho, I., Glenn, G. M., Dubovsky, F., & Madhi, S. A.
Affiliations
  • Novavax (United States) (US)
  • South African Medical Research Council (ZA)
  • University of the Free State (ZA)
  • University of KwaZulu-Natal (ZA)
  • University of the Witwatersrand (ZA)
  • Setshaba Research Centre (ZA)
  • Centre for the AIDS Programme of Research in South Africa (ZA)
  • From Novavax, Gaithersburg, MD (V.S., L. Fries, S.C.-C., M.Z., C.B., G.A., E.F., J.S.P., A.R., S.N., I.C., G.M.G., F.D.); and the South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences (S.B., V.B., A.L.K., A.O.-J., A.T., S.A.M.), Wits Reproductive Health and HIV Institute (L. Fairlie, G.B.), University of the Witwatersrand, and Soweto Clinical Trials Centre (Q.B., A.E.B.), Johannesburg, Josha Research Centre, Bloemfontein (Z.H., J.J.L., S.F.), the Paediatric Infectious Diseases Unit (M.A., R.M.), the Respiratory and Critical Care Unit (U.L., N.L.), the Department of Obstetrics and Gynaecology (D.M.), Centre for the AIDS Programme of Research in South Africa (S.H.), and Kwazulu–Natal Research Innovation and Sequencing Platform (T.O.), Nelson R. Mandela School of Medicine, University of KwaZulu–Natal, Durban, the Setshaba Research Centre, Tshwane (M.S.L.M., A.P., K.A.), the Limpopo Clinical Research Initiative, Rustenburg (L. Fouche, P.-L....
  • University of Pretoria (ZA)
  • University of Cape Town (ZA)
  • Clinical Trial Center Maastricht (NL)
Corresponding author
Shinde, Vivek
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2021-05-20
Volume
384
Issue
20
Pages
1899-1909
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2103055
PMC
PMC8091623
OpenAlex
W3157709232
Cited by
625
References
19
Citations by year
2026: 10 · 2025: 19 · 2024: 46 · 2023: 97 · 2022: 229 · 2021: 221 · 2020: 2
FWCI
47.03
Type
journal article
Language
en
Open access
Licence
Locations
  • New England Journal of Medicine (publishedVersion, cc-by)
  • medRxiv (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • UpSpace Institutional Repository (University of Pretoria) (submittedVersion)
Funders
Novavax
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
NVX-CoV2373, COVID-19 vaccines, vaccine efficacy, nanoparticle vaccine, HIV-infected adults, HIV-negative individuals, neutralizing antibodies, CD4+ T cell responses, reactogenicity, South Africa, Omicron variant
MeSH terms
Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, COVID-19 Serological Testing, Adolescent, Adult, Aged, Aged, 80 and over, Double-Blind Method, HIV Seropositivity, Humans, Middle Aged, South Africa, HIV Seronegativity, Young Adult, Antibodies, Neutralizing

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