Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents
Authors: Áñez Germán , Dunkle Lisa M. , Gay Cynthia L. , Kotloff Karen L. , Adelglass Jeffrey M. , Essink Brandon , Campbell James D. , Cloney-Clark Shane , Zhu Mingzhu , Plested Joyce S. , Roychoudhury Pavitra , Greninger Alexander L. , Patel Nita , McGarry Alice , Woo Wayne , Cho Iksung , Glenn Gregory M. , Dubovsky Filip ,   2019nCoV-301–Pediatric Expansion Study Group, Andersen James , Fearon Szheckera , Negron Rosa , Medina Amy , Figueroa Colleen , Smith Courtney , Rankin Bruce , Hill John M. , Shinn Steven , Rajasekhar Vivek , Nash Marshall , Affan Ashraf , Acevedo Armando , Monteagudo Can Alina , Rodriguez Hector , Zagales Israel , Prieto Christine , Hernandez Diaz Lizz , Hale Max , Farr Patrick , French Liesel , Goldsmith Teresa , Warmack James , Murphy Bailey , Hartvickson Robyn , Dunlavy Brooke , Glover Richard , Grant Amber , Holderman Troy , Slechta Stacy , Poling Terry , Klein Terry , Klein Thomas , Klein Tracy , Pinkham Sarah , Lassiter Shannen , Jandali Imad , Belavilas Maryam , Daniels David , Leonard Katie , Vetter Abigail , Rich Toni , Arora Samir , Cannon Grazia , Guduri Sridhar , Lingel Alandra , Moore Veronica , Wilcox Sarah , Gorman Richard , Horwith Gary , Mason Robin , Chu Laurence , Listz Michelle , Box Lamar , Duran Cindy , Knight Isaiah , Davis Katherine , Seger William , Villegas John , Seger Ben , Loudermilk Virginia , Reyes Ruth , Kim Anthony , Daly Wendy C , Becherer Rebecca , Cornett Denver , Dick Karen , Downs Kimberly , Hall Pamela , Brandon Donald M. , Davis William B. , Lawler Daniel T. , Stevens Cindy , Walter Karl , Rios Michelle , Schwartz Howard , Sanchez-Crespo Nelia , Beltron Thelma , Schwartz Jennifer , Balebona Patricia , Rivera Beatriz , Garcia Barbara , Turley Christine B. , McWilliams Andrew , Esinhart Tiffany , Montoya Natasha , Huskey Shamika , Paul Leena , Dever Michael E. , Shah Mitul , Delgado Michael , Scott Tameika Scott , Brown Patricia , Padilla Americo , Usdan Lisa S. , McGill Lora J. , Arnold Valerie K. , Scatamacchia Carolyn , Anthony Codi , Presley Robyn , Sharp Stephan , Caldwell Michael , Schipani Linda , Ulrich Allison , Tidwell Wendy , Cox Stacy Lynn , Levin Michael , Gass Julia , Kulic Marcy , Rodriguez Eduardo , Corea Jessica , Dansbee Sierra , Delgado John , Ostovar Jaleh , Kuehl Audrey , Smiley Sarah , Hamlin Danuel , Taucher Ben , Tangeman Cayce , Davis Yvonne , Armetta Vanessa , Love Mary , Summers David , Etheridge J. Bruce , Salazar Teresita , David Femina , Vitug Filipinas , Guevarra Amiel , Ramirez Noemi , Ackerman Ronald , Ackerman Jamie , Aristy Florida , Corey Lawrence , Neuzil Kathleen M , Gelderblom Huub G , Ketter Nzeera , Sopher Carrie , Miller Vicki E. , Starr Amy , Guerrero Sonia , Baig Madiha , Jamil Maryam , Motiwala Husain , Palanpurwala Khozema , Murry Monica , Starr Amy Starr, MD, , Tonti Meghan , Wischnewsky Rebecca , Martin Earl , Paliwal Yogesh K. , Paliwal Amit , Gordon Sarah , Edwards Krystle , Montano-Pereira Cynthia , Campos Michael , Freeman George H. , Harmon Esther Laverne , Cross Marshall A. , Sales Kacie , Gular Catherine Q. , Ley Joseph , Donoho Amanda , Hunt Kimberley , Lewis Donald , Tipton Stephanie , Whitaker Emily , Jacqmein Jeffry , Bowers Maggie , Robison Dawn , Mosteller Victoria , Garvey Janet , Fierro Carlos , Easley Mary , Thompson Amy Thompson, MD, , Barker Heather , Zari Mazen , Moore Karol , Finn Daniel , Blackman Lindsay , Block Stanley , Denton Christal , Osborn Martha , Smith Robert , Griffin Carl P. , Schnitz William , Cornelison Raymond , Lopez Linda , Hamilton Kim , Calloway Kim , Musante David B. , Silver William P. , Belhorn Linda R. , Viens Nicholas A. , Dellaero David , Wilkers Elizabeth , Jeanfreau Robert , Johnson Nicki , Bazan Estafania , Roys Davilyn , Darden Steven , Jeanfreau Susan , Matherne Paul G. , Caldwell Amy , Stahl Jessica , Guttierrez Nicole , Beeks Cassandra , Eder Frank , Little Ryan , Owen Susan , Shaw Heather , Tarbox John , Engler Victoia , Gray Roni , Raiser Fritz , Wilson Christine , Nemecek Tiffany , Harrington Hannah , Harper Charles , Johnson Torie , Nutsch Chelsie , Eppenbach Sally , Lewis Wendell , Mace Katlyn , Perilloux Brannon C , Dedon Christopher , Cook Lori , Zedlitz Zedlitz , Srinivasan Vasavi , Melner Paige , Sextor Joanna , Long Jessica , Palumbo Francis , Myers Devon , Vleck Caroline , Warfield Peter , Beresnev Tatiana , Jahromi Maryam , Marovich Mary A. , Hutter Julia , Nason Martha , Leibowitz Mark , Morales Fernanda , Delgado Mike , Sanchez Rosario , Vega Norma , Albert Gary , Coston Erin , Desai Chinar , Dunbar Haoua , Eickhoff Mark , Entzminger-Sneed Renee , Garcia Jenina , Kautz Margaret , Lee Angela , Lewis Maggie , Newingham Patrick , Price-Abbott Patty , Reed Patty , Cerenze Short Kimberly , Vegas Diana , Wilkinson Bethanie , Smith Katherine , Fried David L. , Haughey Lynne A. , Stanton Ariana C. , Freeman Monica , DiFazio Jacqueline , Langlois Courtney , Retino Rosario , Deniz Alexis , Paiva Wendy , Pajarillaga Leonel , Pyio Lisa , Torres Lendy , Wisman Paul , Armengol Carlos , Bouber Gemia , Bressler Peggy , Brown Alaina , Dorsey Candyce , Grunstra Bernard , Dye Amy Dye, , Gilmer Olds Shelby , Bullen Joshua , Roark Miranda , Eller Jennie , Barranco-Santana Elizabeth , Rodriguez Jessica , Mendoza Rafael , Ruperto Karen , Olivieri Odette , Ocaña Enrique , Palchick Bryce , Bennett Nathan , Sobrosky Sarah , Gates Michael , Klutch Suzanne , Martier Jessica , Cruz Marilou , Vu Hoang-Chuing , Serrano Janet , Martinez Valerie , Cruz Marc , Sligh Teresa S. , Desai Parul , Huynh Vincent , Lopez Carlos , Mendoza Erika , Chughtai Waseem , Sathe Anuja , Fox Pamela , Davis Matthew G. , Foley Jennifer , Kane Shelly , Glod Cassidy , Wuilliez Marissa , Purcell Abigail , Senders Shelly , Jeffrey Ashley , Fackelmann Christopher , Jezerinc Nicholas , Fillioe Caitlin , Hudec Timothy , Fogarty Charles , Crockford Nicole , Jones Jami , Mccauley Connie , Yeisley Sherry , Fogarty Alison , Logan Douglas , Gebhardt Bruce C. , Mangu Padma N. , Beck Schroeck Debra , Kumar Davit Rajesh , Hennekes Gayle D. , Wadsworth Larkin Tyler , Marafioti Horacio , Dang Lyly , Clement Lauren , Berry Jennifer , Akinsola Adebayo , Baetista Gabriela , Arimah Baba , Dover Sheree , Hernandez Leslie , Herrera Susan , Etokhana Kenneth , De La Cruz Nathaniel , Fajardo Xavier , Galaviz Veronica , Ruiz Meranda , Diaz Tony , Garcia-Fragoso Veronica , Becerra Maria Gabriela , Mckeown Cecilia , Holloway Lisa , Montero Stacey , Kowalsi Tracy , Cohen Stuart H. , Ruiz Monica , Boswell Dean M. , Robison Elizabeth E. , Reynolds Trina L. , Neumeister Sonja , Campbell Thomas B. , Fiorillo Suzanne , Pitotti Rebecca , Riedel Anderson Victoria , Castillo Mancilla Jose , Le Nga , Tapia Milagritos , Neuzil Kathleen , Berry Andrea , Hammershaimb E. Adrienne , MacBryde Rosa , Florescu Diana F , Starlin Richard , Kline David , Zimmer Andrea , Abbas Anum , Wilson Natasha , Hoffman Erin , Pastrana Medina Carolina , Pedersen Susan , Tipton Mandy , Burbank Alison , Hernandez Michelle , Thompson Peyton , Willis Zachary , Eron Joseph , Coombs Robert W. , Goecker Erin A. , Huang Yunda , Fong Youyi , Buynak Robert J. , Webb Angella , Rivas Rena , Andree Stephanie , McNeal Rachel , Smith Megan , Kasarjian Julie , Kirstein Judith , Foster Krista , Abels Nicole , Lopez Brandy , Rajania Crystle , Rhee Margaret , Jones Gabrielle , Billups Alanna , Boggan Jane , Roadman Denise , Blazy Celeste , Shaw Marian E. , Turner Mark A. , Huffine Cory J. , Huffine Esther S. , Coon Raymond , Hanson Jacqueline , Waters Michael , Zepeda Karla , Overcash Scott , Coslet Jordan , Tovar Dalia , Lee Kia , Koch Mark , Escamilla Norma , Luna Lydia , Mcleod Erin , Dykes Kathryn , Ake Julie A. , Husseman Michael , Fennell Janes , Gilsoul Jennifer , Hoki Robert , MacDonald Ashley , Lobato Mia , Silas Peter , Hawkes Cody , Cooper Jennifer , Nelson Jennifer , Twitchell Jerica , Steil Kenneth , DeJesus Mildred , Gilbert LaShonda , Goldsmith Carey , Gustilo Maria , Jones Jaimi , McKenzie Mark , Deese Teresa , Earwood Mitsi , Leathers Vickie , Sproles Diane , Marques Obadias 
Published: April 2023

ImportanceGreater 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.ObjectiveTo evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.Design, Setting, and ParticipantsThe 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.InterventionsParticipants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.Main Outcomes and MeasuresSerologic 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.ResultsAmong 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 RelevanceThe 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 RegistrationClinicalTrials.gov Identifier: NCT04611802