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

  1. Tushar Tewari
  2. George Armah
  3. Nigel A. Cunliffe
  4. Caroline C. Chisenga
  5. Desiree Witte
  6. Vida Kukula
  7. Khuzwayo C. Jere
  8. Michelo Simuyandi
  9. Susan Damanka
  10. Edson Mwinjiwa
  11. Katayi Kazimbaya
  12. Frank Atuguba
  13. John Williams
  14. Roma Chilengi
  15. Joanne Csedrik
  16. Chris Gast
  17. Alan Fix
  18. Stan Cryz
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Abstract

Background

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.

Methods

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 8,200 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.

Results

4,055 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=3,477) 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).

Conclusions

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.

Highlights

  • The TV P2-VP8 vaccine candidate was safe and immunogenic.

  • TV P2-VP8 was inferior to ROTARIX® in preventing severe rotavirus gastroenteritis.

  • Study provides insight to guide future development of rotavirus vaccine candidates.

Article activity feed

  1. Version published to 10.1101/2025.09.15.25335434 on medRxiv