Immunogenicity and safety of Institut Pasteur du Cambodge (IPC) and updated Thai Red Cross (UTRC) intradermal rabies vaccine regimens among healthy adults in India: A phase 4, open label, equivalence randomised controlled trial

@article{thangaraj2026immunogenicity,
  title = {{Immunogenicity and safety of Institut Pasteur du Cambodge (IPC) and updated Thai Red Cross (UTRC) intradermal rabies vaccine regimens among healthy adults in India: A phase 4, open label, equivalence randomised controlled trial}},
  author = {Jeromie Wesley Vivian Thangaraj and Padinjaremattathil Thankappan Ullas and Balaji Dagadu More and Lokesh Shanmugam and Saravanakumar Velusamy and Dinesh Gopal and Subashri Ramamoorthy and Kanagasabai Kaliaperumal and Mugunthan N. M and Sandhya Arunachalam and Ramaprabha Ramachandran and Gopinath Ramakrishnan and Suresh Arunachalam and Vijay Vidhyakar J. M and Ganeshnee Anthuvan Valli and Siddharth Pugalendhi and Sabarinathan Ramasamy and Karunakaran T and Mohamed Hanifah and Sam Joy and Anoop Velayudhan and Suganya Egambaram and Ala Saritha and Manju Rahi and Simmi Tiwari and Vijay Parashramji Bondre and Manoj V. Murhekar and the Rabies Vaccine Immunogenicity Trial (RVIT) study group},
  journal = {PLOS Medicine},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pmed.1005079},
  url = {https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005079},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Immunogenicity and safety of Institut Pasteur du Cambodge (IPC) and updated Thai Red Cross (UTRC) intradermal rabies vaccine regimens among healthy adults in India: A phase 4, open label, equivalence randomised controlled trial
AU  - Jeromie Wesley Vivian Thangaraj
AU  - Padinjaremattathil Thankappan Ullas
AU  - Balaji Dagadu More
AU  - Lokesh Shanmugam
AU  - Saravanakumar Velusamy
AU  - Dinesh Gopal
AU  - Subashri Ramamoorthy
AU  - Kanagasabai Kaliaperumal
AU  - Mugunthan N. M
AU  - Sandhya Arunachalam
AU  - Ramaprabha Ramachandran
AU  - Gopinath Ramakrishnan
AU  - Suresh Arunachalam
AU  - Vijay Vidhyakar J. M
AU  - Ganeshnee Anthuvan Valli
AU  - Siddharth Pugalendhi
AU  - Sabarinathan Ramasamy
AU  - Karunakaran T
AU  - Mohamed Hanifah
AU  - Sam Joy
AU  - Anoop Velayudhan
AU  - Suganya Egambaram
AU  - Ala Saritha
AU  - Manju Rahi
AU  - Simmi Tiwari
AU  - Vijay Parashramji Bondre
AU  - Manoj V. Murhekar
AU  - the Rabies Vaccine Immunogenicity Trial (RVIT) study group
PY  - 2026
DA  - 2026/10/29
JO  - PLOS Medicine
DO  - 10.1371/journal.pmed.1005079
UR  - https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005079
AB  - Background: Shorter rabies post-exposure prophylaxis (PEP) regimens could improve compliance and access by reducing the number of clinic visits and vaccine requirement per patient. We compared the immunogenicity and safety of a 1-week intradermal Institut Pasteur du Cambodge (IPC) regimen with a 1-month intradermal Updated Thai Red Cross regimen (UTRC) using two rabies vaccines widely used in India: Purified Chick Embryo Cell vaccine (PCECV) and the Purified Vero Cell Rabies vaccine (PVRV). Methods and findings: We conducted a phase 4, single-centre, open-label randomised controlled equivalence trial among adult healthy volunteers. Participants were block randomised (1:1:1:1) to receive either the IPC (Days 0, 3, 7) or UTRC (Days 0, 3, 7, 28) intradermal regimen with either PCECV or the PVRV. Rabies virus neutralizing antibody (RVNA) titres were measured up to 1 year. The primary objective of the trial was to determine the immunogenicity of the Intradermal abridged Cambodia regimen with updated intradermal Thai red cross regimen using two different vaccine types among healthy volunteers in India. The primary outcome was geometric mean concentration ratios (GMR) of RVNA on day 42, assessed separately for each vaccine type. Equivalence for each vaccine was predefined as the entire 95% confidence interval for GMR lying between 0.72 and 1.04. The secondary outcomes included proportion of participants with RVNA titres >= 0.5 IU/mL on Days 14, 28, 42, 90, 180, and 365 and vaccine safety. Between October 10, 2023, and December 23, 2023, 400 participants were randomly assigned (100 per group) to PCECV-IPC, PCECV-UTRC, PVRV-IPC, and PVRV-UTRC. 362 (90.5%) completed PEP regimen and blood draw on day 42. In the prespecified modified intention-to-treat analysis, the Day 42 GMR (IPC vs UTRC) was 0.59 (95% CI: 0.47–0.75) for PCECV and 0.76 (95% CI: 0.61–0.95) for PVRV, which did not meet the prespecified equivalence criterion. All participants, irrespective of baseline serostatus, in four groups had RVNA titres ≥0.5 IU/ml at every assessment from day 14–1 year. Adverse events were similar between regimens and mostly mild. There are important limitations in this study. Nearly one-quarter of participants had baseline RVNA titres ≥0.5 IU/mL despite exclusion of participants with a reported history of rabies vaccination or dog bite, suggesting unrecognised prior immunological priming that may have influenced GMC estimates. As the trial was conducted among healthy volunteers rather than people receiving PEP after animal bites, the findings may not fully reflect vaccine performance in routine post-exposure settings. Conclusion: The IPC regimen did not meet the prespecified equivalence criterion compared to UTRC. All participants achieved RVNA titres ≥0.5 IU/ml indicative of seroprotection from day 14 till 1 year. Policy decisions regarding replacement of UTRC should consider these immunogenicity findings together with compliance, cost, and vaccine availability. Trial Registration: The trial was registered with the Clinical Trial Registry – India (CTRI/2023/10/058418). URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=OTAxMDA=&Enc=&userName=). Why was this study done?: What did the researchers do and find?: What do these findings mean?: In a phase 4 equivalence trial, Jeromie Thangaraj and colleagues compare the immunogenicity and safety of a one-week versus a one-month rabies vaccine regimen.
SN  - 1549-1676
ER  -