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

Vivek Shinde, Sutika Bhikha, Zaheer Hoosain, Moherndran Archary, Qasim Bhorat, Lee Fairlie, Umesh Lalloo, Mduduzi S L Masilela, Dhayendre Moodley, Sherika Hanley, Leon Fouche, Cheryl Louw, Michele Tameris, Nishanta Singh, Ameena Goga, Keertan Dheda, Coert Grobbelaar, Gertruida Kruger, Nazira Carrim-Ganey, Vicky Baillie, Tulio de Oliveira, Anthonet Lombard Koen, Johan J Lombaard, Rosie Mngqibisa, As'ad E Bhorat, Gabriella Benadé, Natasha Lalloo, Annah Pitsi, Pieter-Louis Vollgraaff, Angelique Luabeya, Aliasgar Esmail, Friedrich G Petrick, Aylin Oommen-Jose, Sharne Foulkes, Khatija Ahmed, Asha Thombrayil, Lou Fries, Shane Cloney-Clark, Mingzhu Zhu, Chijioke Bennett, Gary Albert, Emmanuel Faust, Joyce S Plested, Andreana Robertson, Susan Neal, Iksung Cho, Greg M Glenn, Filip Dubovsky, Shabir A Madhi, 2019nCoV-501 Study Group, Nasreen Abrahams, Khatija Ahmed, Gary Albert, Moherndran Archary, Vicky Baillie, Gabriella Benadé, Chijioke Bennett, Sutika Bhikha, As'ad Ebrahim Bhorat, Qasim Bhorat, Raziya Bobat, Michiel Andries Buys, Nazira Carrim-Ganey, Sphiwe Cebekhulu, Janice Chen, Iksung Cho, Shane Cloney-Clark, Tulio de Oliveira, Chinar Desai, Alicia Desmond, Marthie de Villiers, Keertan Dheda, Filip Dubovsky, Amyneline Engelbrecht, Aliasgar Esmail, Yakub Moosa Essack, Lee Fairlie, Emmanuel Faust, Jamie Fiske, Leon Fouche, Sharne Foulkes, Lou Fries, Muhammed Ameen Fulat, Zakir Gaffoor, Nadia Gangat, Hennie Geldenhuys, Greg M Glenn, Ameena Goga, Amina Goondiwala, Vani Govender, Coert Grobbelaar, Tony Guiteau, Sherika Hanley, Jose Heino-Kasbergen, Zaheer Hoosain, Aylin Oommen Jose, Vandana Joshi, Dishiki Jenny Kalonji, Akhona Kamalu, Faeeza Kana, Margaret Kautz, Ntuthuko Khumalo, Girisha Kistnasami, Anthonet Lombard Koen, Gertruida Kruger, Natasha Lalloo, Umesh Lalloo, Maggie Lewis, Johan J Lombaard, Cheryl Louw, Angelique Luabeya, Shabir A Madhi, Edson Makambwa, Mookho Malahleha, Mduduzi S L Masilela, Lenah Masombuka, Michael J Massare, Sajeeda Mawlana, Linda Mbuthini, Mbalenhle Mbuyisa, Carey L Medin, Simon Mendelsohn, Val Mikhailovski, Sibongile Mncube, Rosie Mngqibisa, Mapule Moloi, Dhayendre Moodley, Nozibusiso Rejoice Mosia, Lynelle Mottay, Susan Neal, Cathy Neate, Minenhle Ngcobo, Thandeka Nkosi, Rashina Nundlal, Suzette Oelofse, Faeezah Patel, Nita Patel, Rubeshan Perumal, Sahir Yusuf Petkar, Friedrich G Petrick, Sundrapragasen Pillay, Annah Pitsi, Joyce S Plested, Patricia Price-Abbott, Patricia Reed, Andreana Robertson, Justin Shenje, Vivek Shinde, Nishanta Singh, Sheleika Singh, Gale Smith, Kathy Smith, Lourtacia Sokhela, Michele Tameris, Asha Thombrayil, Danellus van der Watt, Pieter-Louis Vollgraaff, Nelisiwe Xaba, Lu Yang, Jiu Zhao, Mingzhu Zhu, Vivek Shinde, Sutika Bhikha, Zaheer Hoosain, Moherndran Archary, Qasim Bhorat, Lee Fairlie, Umesh Lalloo, Mduduzi S L Masilela, Dhayendre Moodley, Sherika Hanley, Leon Fouche, Cheryl Louw, Michele Tameris, Nishanta Singh, Ameena Goga, Keertan Dheda, Coert Grobbelaar, Gertruida Kruger, Nazira Carrim-Ganey, Vicky Baillie, Tulio de Oliveira, Anthonet Lombard Koen, Johan J Lombaard, Rosie Mngqibisa, As'ad E Bhorat, Gabriella Benadé, Natasha Lalloo, Annah Pitsi, Pieter-Louis Vollgraaff, Angelique Luabeya, Aliasgar Esmail, Friedrich G Petrick, Aylin Oommen-Jose, Sharne Foulkes, Khatija Ahmed, Asha Thombrayil, Lou Fries, Shane Cloney-Clark, Mingzhu Zhu, Chijioke Bennett, Gary Albert, Emmanuel Faust, Joyce S Plested, Andreana Robertson, Susan Neal, Iksung Cho, Greg M Glenn, Filip Dubovsky, Shabir A Madhi, 2019nCoV-501 Study Group, Nasreen Abrahams, Khatija Ahmed, Gary Albert, Moherndran Archary, Vicky Baillie, Gabriella Benadé, Chijioke Bennett, Sutika Bhikha, As'ad Ebrahim Bhorat, Qasim Bhorat, Raziya Bobat, Michiel Andries Buys, Nazira Carrim-Ganey, Sphiwe Cebekhulu, Janice Chen, Iksung Cho, Shane Cloney-Clark, Tulio de Oliveira, Chinar Desai, Alicia Desmond, Marthie de Villiers, Keertan Dheda, Filip Dubovsky, Amyneline Engelbrecht, Aliasgar Esmail, Yakub Moosa Essack, Lee Fairlie, Emmanuel Faust, Jamie Fiske, Leon Fouche, Sharne Foulkes, Lou Fries, Muhammed Ameen Fulat, Zakir Gaffoor, Nadia Gangat, Hennie Geldenhuys, Greg M Glenn, Ameena Goga, Amina Goondiwala, Vani Govender, Coert Grobbelaar, Tony Guiteau, Sherika Hanley, Jose Heino-Kasbergen, Zaheer Hoosain, Aylin Oommen Jose, Vandana Joshi, Dishiki Jenny Kalonji, Akhona Kamalu, Faeeza Kana, Margaret Kautz, Ntuthuko Khumalo, Girisha Kistnasami, Anthonet Lombard Koen, Gertruida Kruger, Natasha Lalloo, Umesh Lalloo, Maggie Lewis, Johan J Lombaard, Cheryl Louw, Angelique Luabeya, Shabir A Madhi, Edson Makambwa, Mookho Malahleha, Mduduzi S L Masilela, Lenah Masombuka, Michael J Massare, Sajeeda Mawlana, Linda Mbuthini, Mbalenhle Mbuyisa, Carey L Medin, Simon Mendelsohn, Val Mikhailovski, Sibongile Mncube, Rosie Mngqibisa, Mapule Moloi, Dhayendre Moodley, Nozibusiso Rejoice Mosia, Lynelle Mottay, Susan Neal, Cathy Neate, Minenhle Ngcobo, Thandeka Nkosi, Rashina Nundlal, Suzette Oelofse, Faeezah Patel, Nita Patel, Rubeshan Perumal, Sahir Yusuf Petkar, Friedrich G Petrick, Sundrapragasen Pillay, Annah Pitsi, Joyce S Plested, Patricia Price-Abbott, Patricia Reed, Andreana Robertson, Justin Shenje, Vivek Shinde, Nishanta Singh, Sheleika Singh, Gale Smith, Kathy Smith, Lourtacia Sokhela, Michele Tameris, Asha Thombrayil, Danellus van der Watt, Pieter-Louis Vollgraaff, Nelisiwe Xaba, Lu Yang, Jiu Zhao, Mingzhu Zhu

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.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1.. Disposition of Participants in the…
Figure 1.. Disposition of Participants in the Trial.
The full analysis set included all participants who were randomly assigned to treatment and received at least one dose, regardless of protocol violations or missing data, and are analyzed according to the trial vaccine group as randomized. This diagram represents the disposition of participants in the trial. Among participants excluded for not meeting inclusion/exclusion criteria: approximately 32% tested HIV-positive on screening, 18% had a history of suspected or diagnosed Covid-19, 11% had an exclusionary chronic disease condition, 9% had exclusionary high or low BMI, 7% could not provide informed consent, and 5% had acute or ongoing illness. Among participants excluded for “other” reasons: approximately 69% were otherwise eligible but had missed the time window for enrollment into a particular stage or cohort; and 23% of “other” did not meet inclusion/exclusion criteria but were recorded under the free text category of “other” (these had a similar distribution of exclusion criteria as those recorded under “not meeting inclusion/exclusion criteria”). The data cutoff date for the primary efficacy analysis was January 8, 2021, which represented a median follow-up of 66 and 45 days after first and second vaccination, respectively. The data cutoff date for the primary safety analysis was January 25, 2021, which included safety data through 35 days after first vaccination in all 968 Stage 1 participants (889 HIV-negative and 79 PLWH). The safety analysis set included all participants who received at least one dose of NVX-CoV2373 or placebo, with participants analyzed according to the treatment actually received. The per-protocol efficacy analysis set (PP-EFF) included baseline seronegative (by anti-spike IgG) participants who received both injection of NVX-CoV2373 or placebo as assigned, had no evidence of SARS-CoV-2 infection (by NAAT or anti-spike IgG) within 7 days after the second vaccination (ie, before Day 28), and had no major protocol deviations affecting the primary efficacy outcome. A second per-protocol efficacy analysis set (PP-EFF-2) was defined in a similar fashion except without the exclusion of baseline seropositive participants to allow for analysis of efficacy in seropositive or all participants, regardless of serostatus. Abbreviations: HIV = human immunodeficiency virus; IgG = immunoglobulin G; NAAT = nucleic acid amplification test; PLWH = people living with HIV; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Figure 2.. Kaplan-Meyer Plots of Efficacy of…
Figure 2.. Kaplan-Meyer Plots of Efficacy of NVX-CoV2373 Against Symptomatic Covid-19, Risk of Symptomatic Covid-19 in Seropositive versus Seronegative Placebo Recipients, and Timing of Endpoint Accrual.
Shown is the cumulative incidence of symptomatic Covid-19. The time period for surveillance of per-protocol symptomatic Covid-19 cases was from at least 7 days after the second dose (ie, Day 28) of NVX-CoV2373 or placebo through the first 2 months of follow-up. Data shown are for the per-protocol efficacy analysis sets (PP-EFF or PP-EFF-2), unless otherwise indicated. A) All participants (HIV-negative and PLWH), baseline seronegative; B) HIV-negative participants, baseline seronegative; C) Placebo participants, baseline seronegative vs baseline seropositive, in the full analysis set (FAS) from Day 0 onwards. The FAS included all participants who were randomly assigned to treatment and receive at least 1 dose, regardless of protocol violations or missing data. D) Per protocol efficacy endpoint accrual relative to distribution of variant as reported in Nextstrain.org. A. All participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set B. HIV-negative participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set C. Placebo participants ONLY (baseline seronegative placebo versus baseline seropositive placebo): primary efficacy endpoint from Day 0 onwards in the full analysis set D. Accrual of Primary Efficacy Endpoints Relative to B.1.351 (501Y.V2) Variant Circulation in South Africa by Time. Source: Nextstrain.org. Freely available under the terms of the GNU Affero General Public License.
Figure 2.. Kaplan-Meyer Plots of Efficacy of…
Figure 2.. Kaplan-Meyer Plots of Efficacy of NVX-CoV2373 Against Symptomatic Covid-19, Risk of Symptomatic Covid-19 in Seropositive versus Seronegative Placebo Recipients, and Timing of Endpoint Accrual.
Shown is the cumulative incidence of symptomatic Covid-19. The time period for surveillance of per-protocol symptomatic Covid-19 cases was from at least 7 days after the second dose (ie, Day 28) of NVX-CoV2373 or placebo through the first 2 months of follow-up. Data shown are for the per-protocol efficacy analysis sets (PP-EFF or PP-EFF-2), unless otherwise indicated. A) All participants (HIV-negative and PLWH), baseline seronegative; B) HIV-negative participants, baseline seronegative; C) Placebo participants, baseline seronegative vs baseline seropositive, in the full analysis set (FAS) from Day 0 onwards. The FAS included all participants who were randomly assigned to treatment and receive at least 1 dose, regardless of protocol violations or missing data. D) Per protocol efficacy endpoint accrual relative to distribution of variant as reported in Nextstrain.org. A. All participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set B. HIV-negative participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set C. Placebo participants ONLY (baseline seronegative placebo versus baseline seropositive placebo): primary efficacy endpoint from Day 0 onwards in the full analysis set D. Accrual of Primary Efficacy Endpoints Relative to B.1.351 (501Y.V2) Variant Circulation in South Africa by Time. Source: Nextstrain.org. Freely available under the terms of the GNU Affero General Public License.
Figure 2.. Kaplan-Meyer Plots of Efficacy of…
Figure 2.. Kaplan-Meyer Plots of Efficacy of NVX-CoV2373 Against Symptomatic Covid-19, Risk of Symptomatic Covid-19 in Seropositive versus Seronegative Placebo Recipients, and Timing of Endpoint Accrual.
Shown is the cumulative incidence of symptomatic Covid-19. The time period for surveillance of per-protocol symptomatic Covid-19 cases was from at least 7 days after the second dose (ie, Day 28) of NVX-CoV2373 or placebo through the first 2 months of follow-up. Data shown are for the per-protocol efficacy analysis sets (PP-EFF or PP-EFF-2), unless otherwise indicated. A) All participants (HIV-negative and PLWH), baseline seronegative; B) HIV-negative participants, baseline seronegative; C) Placebo participants, baseline seronegative vs baseline seropositive, in the full analysis set (FAS) from Day 0 onwards. The FAS included all participants who were randomly assigned to treatment and receive at least 1 dose, regardless of protocol violations or missing data. D) Per protocol efficacy endpoint accrual relative to distribution of variant as reported in Nextstrain.org. A. All participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set B. HIV-negative participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set C. Placebo participants ONLY (baseline seronegative placebo versus baseline seropositive placebo): primary efficacy endpoint from Day 0 onwards in the full analysis set D. Accrual of Primary Efficacy Endpoints Relative to B.1.351 (501Y.V2) Variant Circulation in South Africa by Time. Source: Nextstrain.org. Freely available under the terms of the GNU Affero General Public License.
Figure 2.. Kaplan-Meyer Plots of Efficacy of…
Figure 2.. Kaplan-Meyer Plots of Efficacy of NVX-CoV2373 Against Symptomatic Covid-19, Risk of Symptomatic Covid-19 in Seropositive versus Seronegative Placebo Recipients, and Timing of Endpoint Accrual.
Shown is the cumulative incidence of symptomatic Covid-19. The time period for surveillance of per-protocol symptomatic Covid-19 cases was from at least 7 days after the second dose (ie, Day 28) of NVX-CoV2373 or placebo through the first 2 months of follow-up. Data shown are for the per-protocol efficacy analysis sets (PP-EFF or PP-EFF-2), unless otherwise indicated. A) All participants (HIV-negative and PLWH), baseline seronegative; B) HIV-negative participants, baseline seronegative; C) Placebo participants, baseline seronegative vs baseline seropositive, in the full analysis set (FAS) from Day 0 onwards. The FAS included all participants who were randomly assigned to treatment and receive at least 1 dose, regardless of protocol violations or missing data. D) Per protocol efficacy endpoint accrual relative to distribution of variant as reported in Nextstrain.org. A. All participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set B. HIV-negative participants (baseline seronegative): primary efficacy endpoint from 7 days after second dose (Day 28) in the per-protocol analysis set C. Placebo participants ONLY (baseline seronegative placebo versus baseline seropositive placebo): primary efficacy endpoint from Day 0 onwards in the full analysis set D. Accrual of Primary Efficacy Endpoints Relative to B.1.351 (501Y.V2) Variant Circulation in South Africa by Time. Source: Nextstrain.org. Freely available under the terms of the GNU Affero General Public License.

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Source: PubMed

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