Journal Article

Safety, immunogenicity, and relative efficacy of a parenteral trivalent rotavirus subunit vaccine candidate (TV P2-VP8) in healthy Ghanaian, Malawian, and Zambian infants

Mwinjiwa, Edson, Cunliffe, Nigel A., Csedrik, Joanne, Cryz, Stan, Kukula, Vida, Jere, Khuzwayo C., Williams, John, Witte, Desiree, Chisenga, Caroline C., Fix, Alan, Kazimbaya, Katayi, Atuguba, Frank, Damanka, Susan, Armah, George, Simuyandi, Michelo, Chilengi, Roma, Gast, Chris, Tewari, Tushar

2026

Overview

While live oral rotavirus vaccines (LORVs) are effective at preventing severe rotavirus gastroenteritis (SRVGE), they perform sub-optimally in the settings with the highest burden. Parenteral rotavirus vaccines could have greater efficacy by bypassing the gut, where interference with LORVs may occur. A novel parenteral rotavirus subunit vaccine (TV P2-VP8) was evaluated in a Phase 3 study for safety, immunogenicity, and relative efficacy in healthy African infants. Participating infants were randomized at 6–8 weeks of age to receive either three doses of TV P2-VP8 intramuscularly (IM) plus oral placebo or two doses of ROTARIX® (oral) plus IM placebo. The trial was designed to enroll a total of 8200 participants in two stages separated by an interim analysis conducted upon accrual of a predetermined number of SRVGE cases. Data at interim analysis indicated a low probability of demonstrating TV P2-VP8 superiority compared to ROTARIX in prevention of SRVGE, and the study was closed early. 4055 infants were enrolled and provided safety data. TV P2-VP8 was safe and well tolerated, with no safety concerns indicated. Virus neutralizing and IgG binding antibody seroresponses to TV-P2-VP8 were detected in most participants. The crude attack rates of SRVGE in the per-protocol population (n = 3477) were 4.51 % (TV P2-VP8) and 2.57 % (ROTARIX). The relative vaccine efficacy (RVE) against SRVGE for TV P2-VP8 was −77.68 % (95 % CI, −162.38, −21.54). The RVE against SRVGE in the first and second year of life was −91.67 % (95 % CI, −199.20, −24.35) and − 31.97 % (95 % CI, −220.37, 44.49), respectively. The RVE against rotavirus gastroenteritis of any severity was −47.78 % (95 % CI, −89.63, −15.59). TV P2-VP8 provided inferior protection against SRVGE compared to ROTARIX. The vaccine candidate was safe, immunogenic, and well-tolerated by infants. Continued efforts are needed to identify alternative rotavirus vaccines with improved efficacy in LMICs. Trial Registration:NCT04010448; PACTR201907491834482. •The TV P2-VP8 vaccine candidate was safe and immunogenic.•Three doses of TV P2-VP8 were inferior to two doses of ROTARIX® in preventing severe rotavirus gastroenteritis.•Study provides insight to guide future development of rotavirus vaccine candidates.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Administration, Oral / Allergy and Immunology / antibodies / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Consent / digestive system / Disease prevention / Double-Blind Method / Effectiveness / Female / Gastroenteritis / Gastroenteritis - prevention & control / Gastroenteritis - virology / Ghana / Humans / Immunogenicity / Immunogenicity, Vaccine / Immunoglobulin G / Immunoglobulin G - blood / Infant / Infants / Injections, Intramuscular / Intestinal obstruction / Licenses / Malawi / Male / Placebos / probability / Relative vaccine efficacy / Review boards / Rotavirus / Rotavirus - immunology / Rotavirus gastroenteritis / Rotavirus Infections - prevention & control / Rotavirus Vaccines - administration & dosage / Rotavirus Vaccines - adverse effects / Rotavirus Vaccines - immunology / Safety / subunit vaccines / Vaccine / Vaccine Efficacy / Vaccines / Vaccines, Attenuated - administration & dosage / Vaccines, Attenuated - adverse effects / Vaccines, Attenuated - immunology / Vaccines, Subunit - administration & dosage / Vaccines, Subunit - adverse effects / Vaccines, Subunit - immunology / Viruses / Zambia