Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC]

Summary

PRIBIVAC will assess a heterologous prime-boost-boost strategy in comparison with a homologous regimen in order to compare short and long-term immunogenicity of different COVID-19 vaccine combinations against the ancestral SARS-CoV-2 as well as different variants of concern (VOCs). Initial phases of the study (Phases A-C) have studied homologous versus heterologous vaccines at the first booster, later phases (Phase D) will study these as the second booster. Hypothesis: One or more heterologous prime-boost-boost COVID-19 vaccine combinations will produce humoral and cellular immunity that is non-inferior to an homologous prime-boost-boost vaccination against wildtype SARS-CoV-2 and/or 1≥ VOC. In Phases A-C of the study the primary 2 dose mRNA vaccine series was defined as 'Prime-boost'. For phase D we will define these 2 doses as 'Prime' and the 3rd vaccine dose as 'Boost'.

Timeline

Start

2021-10-12

Primary completion

2023-06-01

Completion

2024-05-07

Outcome

Missed primary endpoint

paper titers were lower with BBV152 (2004 IU/mL; 95 % confidence interval [CI], 1132-3548) vs mRNA (26,669 IU/mL; 95 % CI, 21,330-33,266; p < 0.0001) PMID 39241318 ↗

Publications

• Background Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10.
• Background Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30.
• Poh XY, Torres-Ruesta A, Yoong T, Wong N, Tan CW, Rouers A, Chavatte JM, Goh YS, Rao S, Chia PY, Ong SWX, Lee TH, Sadarangani SP, Lin RJH, Neo V, Kam IKJ, Huang Y, Hor PX, Loh CY; PRIBIVAC study group; Yeoh AY, Lim DRX, Chia W, Ren EC, Lin RTP, Fong SW, Renia L, Lye DC, Wang LF, Ng LFP, Young BE. Immunogenicity of mRNA vs. BBV152 vaccine boosters against Omicron subvariants: Final results from Phase B of the PRIBIVAC study, a randomized clinical trial. Vaccine. 2024 Nov 14;42(25):126275. doi: 10.1016/j.vaccine.2024.126275. Epub 2024 Sep 5.
• Goh YS, Fong SW, Hor PX, Loh CY, Wang B, Salleh SNM, Ngoh EZX, Lee RTC, Poh XY, Rao S, Chia PY, Ong SWX, Lee TH, Lim C, Teo J, Pada S, Sun LJ, Ong DLS, Somani J, Lee ES, Maurer-Stroh S, Wang CI, Leo YS, Lye DC, Young BE, Ng LFP, Renia L; NCID Study Group; COVID-19 Cohort Study Group. Variant-Specific IgA Protects Against Omicron Infection. J Infect Dis. 2024 Aug 16;230(2):e287-e291. doi: 10.1093/infdis/jiad525.
• Poh XY, Lee IR, Lim C, Teo J, Rao S, Chia PY, Ong SWX, Lee TH, Lin RJH, Ng LFP, Ren EC, Lin RTP, Wang LF, Renia L, Lye DC, Young BE. Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC]. Trials. 2022 Jun 16;23(1):498. doi: 10.1186/s13063-022-06345-2.
• Poh XY, Tan CW, Lee IR, Chavatte JM, Fong SW, Prince T, Hartley C, Yeoh AYY, Rao S, Chia PY, Ong SWX, Lee TH, Sadarangani SP, Lin RJH, Lim C, Teo J, Lim DRX, Chia W, Hiscox JA, Ng LFP, Ren EC, Lin RTP, Renia L, Lye DC, Wang LF, Young BE. Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial. Clin Infect Dis. 2022 Dec 19;75(12):2088-2096. doi: 10.1093/cid/ciac345.

Drugs

Indications