This page provides an accessible overview of the published study. Readers should consult the original peer-reviewed article for the complete protocol, statistical methods, tables, supplementary material, limitations and author declarations.
Publication Overview
Title: Safety and immunogenicity of Biological E’s typhoid conjugate vaccine TYPHIBEV® concomitantly administered with measles rubella vaccine: a phase IV prospective, multicenter study
Journal: IJID Regions
Volume and article number: Volume 15 (2025), Article 100611
DOI: 10.1016/j.ijregi.2025.100611
Trial registration: CTRI/2022/02/040285
Study type: Phase IV, prospective, multicentre, open-label study with a randomised infant co-administration comparison
Setting: Eleven study sites across India
Population: 1,252 healthy participants aged 6 months to 45 years
Investigational vaccine: TYPHIBEV®, Biological E’s Vi-CRM197 typhoid conjugate vaccine
Co-administered vaccine: Measles-rubella vaccine in infants aged 9–12 months
King George Hospital role: King George Hospital, Visakhapatnam was one of the participating study sites. Bheemisetty S. Chakravarthy is listed as a co-author with the King George Hospital affiliation.
Why This Study Matters
Typhoid fever remains a major infectious-disease burden, especially in settings affected by unsafe water, inadequate sanitation and rising antimicrobial resistance. Typhoid conjugate vaccines are important because conjugation of the Vi polysaccharide antigen to a carrier protein can generate T-cell-dependent immune responses and immune memory, including in young children.
An important programme question is whether a typhoid conjugate vaccine can be administered at the same visit as measles-rubella vaccine without creating new safety concerns or reducing the immune response to either vaccine. This is especially relevant because the first measles-containing vaccine is commonly scheduled during late infancy, when typhoid conjugate vaccine may also be considered.
About TYPHIBEV®
TYPHIBEV® is a monovalent typhoid Vi-CRM197 glycoconjugate vaccine developed by Biological E. Each 0.5 mL dose contains Vi polysaccharide conjugated to the CRM197 carrier protein and is administered intramuscularly.
The vaccine had previously undergone phase I and phase II/III evaluation. This phase IV study extended the safety database and specifically examined co-administration with measles-rubella vaccine in infants.
What does “immune non-interference” mean? When two vaccines are given together, each should still generate an adequate immune response. In this study, the measles antibody response after TYPHIBEV® plus MR was compared with MR alone, and the anti-Vi response after TYPHIBEV® plus MR was compared with TYPHIBEV® alone.
Study Design
| Design Element | Detail |
|---|---|
| Phase | Phase IV |
| Design | Prospective, multicentre, open-label safety and immunogenicity study |
| Sites | Eleven sites across India |
| Total enrolment | 1,252 healthy participants |
| Age range | 6 months to 45 years |
| Age subset 1 | 6 months to <2 years; n=532 |
| Age subset 2 | 2 years to <18 years; n=360 |
| Age subset 3 | 18 to 45 years; n=360 |
| Randomised infant comparison | 400 infants aged 9–12 months allocated 1:1 to TYPHIBEV® + MR or MR alone |
| Additional infant group | 132 participants aged 6 months to <2 years received TYPHIBEV® alone |
| Primary objective | Safety and tolerability of TYPHIBEV® from 6 months to 45 years |
| Secondary objective | Assessment of potential immune interference during TYPHIBEV® and MR co-administration |
| Safety follow-up | Solicited reactions for 7 days; unsolicited, serious and medically attended adverse events throughout follow-up |
Study Flow
1,252 participants enrolled
- 6 months to <2 years: 532 participants
- 200 received TYPHIBEV® + MR
- 200 received MR alone
- 132 received TYPHIBEV® alone
- 2 to <18 years: 360 participants received TYPHIBEV®
- 18 to 45 years: 360 participants received TYPHIBEV®
Anti-measles IgG was assessed at Day 28 and anti-Vi IgG at Day 42 in the relevant infant groups. Safety was assessed across all vaccinated participants.
Safety Findings
Among the 1,052 participants who received TYPHIBEV®, either alone or with MR, 139 participants (13.21%) reported at least one adverse event. Most events were solicited and occurred during the first seven days after vaccination.
| Safety Finding | Result |
|---|---|
| Most frequent adverse event | Injection-site pain |
| Other common events highlighted in the abstract | Pyrexia and injection-site swelling |
| Unsolicited adverse events | Reported in 12 TYPHIBEV® recipients (1.14%) |
| Medically attended adverse events | Eight events among TYPHIBEV® recipients (0.8%) |
| Serious adverse event | One hospitalisation for fever, loose stools and vomiting in a 9-month-old infant; assessed as unrelated to the study vaccines |
| Deaths or vaccine-related discontinuations | None reported |
In the 9–12 month infant comparison, adverse events occurred in 11.0% of participants who received TYPHIBEV® plus MR and 17.5% of those who received MR alone. The publication concluded that no safety signal was identified.
Immunogenicity Findings
Immune responses were assessed in the infant groups most relevant to co-administration. The descriptive findings showed similar measles and typhoid seroprotection when the vaccines were given together compared with administration of the corresponding vaccine alone.
| Immune Outcome | Co-administration Group | Comparison Group |
|---|---|---|
| Measles seroprotection at Day 28 | 80.61% — TYPHIBEV® + MR | 80.90% — MR alone |
| ≥4-fold rise in anti-measles IgG | 63.27% — TYPHIBEV® + MR | 59.8% — MR alone |
| Typhoid seroprotection at Day 42 | 91.24% — TYPHIBEV® + MR | 90.15% — TYPHIBEV® alone |
| ≥4-fold rise in anti-Vi IgG | 96.39% — TYPHIBEV® + MR | 96.97% — TYPHIBEV® alone |
Geometric mean antibody concentrations increased after vaccination in all relevant groups. Anti-measles IgG concentrations at Day 28 and anti-Vi IgG concentrations at Day 42 were comparable between the co-administration and single-vaccine groups.
Evidence-supported interpretation: The study found no evidence that concomitant administration of TYPHIBEV® and measles-rubella vaccine reduced the measured immune response to either the measles antigen or the Vi typhoid antigen.
Clinical and Public Health Significance
The findings support the practical possibility of administering TYPHIBEV® at the same visit as measles-rubella vaccine in late infancy. Co-administration can reduce the number of separate clinic visits, potentially improve vaccine uptake and make immunisation delivery more efficient.
However, the study evaluated safety and immunogenicity—not direct protection against clinical typhoid disease. The results therefore support immune compatibility and tolerability but should not be interpreted as a direct vaccine-effectiveness estimate.
Study Limitations
- The sample size was not large enough to detect extremely rare adverse events.
- Post-marketing surveillance and large observational studies remain important for long-term safety monitoring.
- Anti-measles responses were measured using an ELISA-based assay rather than the preferred plaque reduction neutralisation test.
- The immune non-interference analysis was primarily descriptive and was not prospectively powered as a formal non-inferiority endpoint.
- Large efficacy or real-world effectiveness studies are still required to measure protection against clinical typhoid.
Role of Andhra Medical College and King George Hospital
King George Hospital, Visakhapatnam, was one of the participating sites in this multicentre Indian study. Bheemisetty S. Chakravarthy is included in the author list with the King George Hospital affiliation.
Note on authorship: The publication identifies Dr. B. S. Chakravarthy as a co-author from King George Hospital. This summary does not attribute overall study leadership, sponsorship or corresponding authorship to him.
Key Takeaways
- This phase IV study enrolled 1,252 participants aged 6 months to 45 years across eleven Indian sites.
- TYPHIBEV® was evaluated for overall safety and for co-administration with measles-rubella vaccine in infants aged 9–12 months.
- Among TYPHIBEV® recipients, 13.21% reported at least one adverse event; most events were early, solicited and mild.
- One serious adverse event occurred and was judged unrelated to vaccination.
- Measles seroprotection was similar after TYPHIBEV® + MR and MR alone.
- Typhoid seroprotection was similar after TYPHIBEV® + MR and TYPHIBEV® alone.
- The authors reported no safety signal and no evidence of immunogenic interference.
- The study did not directly measure clinical efficacy against typhoid disease.
- Dr. B. S. Chakravarthy is a co-author from the King George Hospital study site.
Original Publication
This webpage is an educational summary. The complete methods, analyses, tables, figures, supplementary information and declarations are available in the original open-access article.
Funding and disclosures: The study received financial support from Biological E Limited. Several authors were employees of Biological E Limited and reported no share ownership; all other authors reported no conflicts of interest. Readers should consult the original publication for the complete author-by-author declarations.
Dr. B. S. Chakravarthy
Professor & Head, Department of Pediatrics
Andhra Medical College & King George Hospital, Visakhapatnam
Co-author — IJID Regions (2025)