Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents
Germán Áñez, Lisa M. Dunkle, Cynthia L. Gay, Karen L. Kotloff, Jeffrey Adelglass, Brandon Essink, James D. Campbell, Shane Cloney-Clark, Mingzhu Zhu, Joyce S. Plested, Pavitra Roychoudhury, Alexander L. Greninger, Nita Patel, Alice McGarry, Wayne Woo, Iksung Cho, Gregory M. Glenn, Filip Dubovsky, 2019nCoV-301–Pediatric Expansion Study Group, James Andersen, Szheckera Fearon, Rosa Negron, Amy Medina, Colleen Figueroa, C. Leslie Smith, Bruce Rankin, John M. Hill, Steven Shinn, Vivek Rajasekhar, Marshall Nash, Ashraf Affan, Armando Acevedo, Alina Monteagudo Can, Hector P. Rodríguez, Israel Zagales, Christine Prieto, Lizz Hernandez Diaz, Max Hale, Patrick Farr, Liesel French, Teresa Goldsmith, James Warmack, Bailey Murphy, Robyn Hartvickson, Brooke Dunlavy, Richard Glover, Amber Grant, Troy Holderman, Stacy Slechta, Terry L. Poling, Terry Klein, Thomas Klein, Tracy Klein, Sarah Pinkham, Shannen Lassiter, Imad Jandali, Maryam Belavilas, David Daniels, Katie E. Leonard, Abigail Vetter, Toni Rich, Samir Arora, Grazia Cannon, Sridhar Guduri, Alandra Lingel, Veronica Moore, Sarah Wilcox, Richard L. Gorman, Gary Horwith, Robín Masón, Laurence Chu, Michelle Listz, Lamar Box, Cindy Duran, Isaiah Knight, Katherine M. Davis, William Seger, John Villegas, Ben Seger, Virginia Loudermilk, Ruth Reyes, Anthony Kim, Wendy C Daly, Rebecca Becherer, Denver Cornett, Karen Dick, Kimberly Downs, Pamela R. Hall, Donald M. Brandon, William B. Davis, Daniel T. Lawler, Cindy Stevens, Karl A. Walter, Michelle Rios, Howard Schwartz, Nelia Sánchez-Crespo, Thelma Beltron, Jennifer Schwartz, Patricia Balebona, Beatriz Rivera
Abstract
Importance: Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents. Objective: To evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents. Design, Setting, and Participants: The NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized. Interventions: Participants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. Main Outcomes and Measures: Serologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety. Results: Among 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation. Conclusions and Relevance: The findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents. Trial Registration: ClinicalTrials.gov Identifier: NCT04611802.