Immunogenicity and Safety of a Dose-Sparing Inactivated Poliovirus Vaccine in India

Publication Overview

Background

Poliovirus has been one of the most feared childhood diseases in human history — a viral illness capable of causing permanent paralysis or death within hours. The Global Polio Eradication Initiative, launched in 1988, has achieved a dramatic reduction in polio burden: from an estimated 350,000 cases annually across more than 125 countries to single-digit numbers of wild poliovirus cases globally.

India achieved a landmark milestone in 2014 when it was officially certified polio-free by the World Health Organization — the result of decades of intensive immunisation campaigns, strong political commitment, and the dedicated work of millions of frontline healthcare workers across the country.

However, maintaining this polio-free status in the face of continuing global risks — including circulating vaccine-derived poliovirus strains and IPV supply constraints — remains an active public health challenge, one that the trial described on this page directly addresses.

Why Dose-Sparing IPV Was Studied

Inactivated poliovirus vaccine (IPV) is a highly effective vaccine that produces strong systemic immunity and protects individuals from paralytic poliomyelitis. Unlike oral poliovirus vaccine (OPV), it cannot revert to a virulent form and cannot cause vaccine-derived poliovirus disease.

As the global eradication programme moves toward phased cessation of oral poliovirus vaccines, IPV has become increasingly central. However, standard full-dose IPV faces two significant practical barriers in many low- and middle-income countries:

• Cost: Full-dose IPV is considerably more expensive to procure than oral poliovirus vaccine, making universal coverage challenging in resource-constrained settings.
• Delivery logistics: Administering IPV at the scale required for population-level immunity — including campaign use — is operationally demanding, particularly in areas with fragile cold chains or limited healthcare infrastructure.

Several countries have responded by adopting fractional or limited-dose regimens of IPV, typically administered intradermally. This approach reduces antigen demand but has its own logistical and immunogenicity considerations.

An alternative approach is the development of an adjuvanted dose-sparing IPV (ds-IPV) — a formulation combining a reduced antigen dose with an adjuvant that enhances the body's immune response. The ds-IPV evaluated in this trial contains approximately one-fourth the antigen content of standard full-dose IPV, potentially reducing both cost and antigen demand without requiring intradermal delivery technique.

Study Design

The trial was designed as a phase 2/3, double-blind, randomised controlled trial conducted across multiple sites in India. This is among the most rigorous designs for evaluating vaccine safety and immunogenicity.

Double-blinding means that participants' parents, site personnel responsible for evaluating study outcomes, and laboratory personnel were unaware of vaccine allocation. The study vaccines were administered using syringes covered with an opaque peel to conceal the vaccine formulation and preserve masking.

Randomisation ensures participants were allocated to intervention and comparator groups by chance, reducing the likelihood that pre-existing differences between groups could explain any observed outcome differences.

Participants and Intervention

The trial enrolled infants across multiple sites in India. Recruitment was conducted in accordance with national regulatory requirements, Good Clinical Practice guidelines, and with informed consent obtained from parents or legal guardians of each participant.

The investigational product was the adjuvanted dose-sparing IPV (ds-IPV) developed in India, containing approximately one-fourth the antigen content of standard full-dose IPV. The adjuvant is designed to compensate for the reduced antigen dose by enhancing the immune response to vaccination.

The trial enrolled healthy infants aged 6–8 weeks at nine tertiary care hospitals across India. All enrolled infants had received a birth dose of bivalent oral poliovirus vaccine (bOPV). Infants with fever or acute infection, or who had previously received or planned to receive any other poliovirus-containing vaccine, were excluded.

Between 23 May 2022 and 13 April 2024, 658 participants were screened. Of these, 648 were eligible and randomly assigned 1:1 to receive either ds-IPV (n=324) or full-dose IPV (n=324). Consent was withdrawn for five participants after randomisation, meaning 643 infants received at least one study vaccine dose: 323 in the ds-IPV group and 320 in the full-dose IPV group.

Both groups received three doses of 0.5 mL by intramuscular route at age 6, 10 and 14 weeks. All participants also received oral rotavirus vaccine and injectable DTwP-HB-Hib and pneumococcal vaccines concomitantly, consistent with India's routine immunisation schedule.

Blood samples were collected at baseline before the first dose and at 28 days after the third dose, for measurement of neutralising antibodies against each poliovirus serotype using a microneutralisation assay. The site staff evaluating study outcomes, participants' parents and the laboratory personnel were all masked to vaccine allocations.

Immunogenicity Findings

Immunogenicity — the ability of a vaccine to induce an immune response — was the primary focus of this trial. For poliovirus vaccines, immunogenicity is assessed by measuring neutralising antibody levels against all three poliovirus serotypes (type 1, type 2 and type 3).

Seroconversion is the proportion of vaccinated infants who develop a detectable antibody response, as defined by the study protocol. The primary outcome was seroconversion for each serotype at 28 days after the third dose. Non-inferiority was defined as a lower bound of the 95% confidence interval for the difference in seroconversion rates (ds-IPV minus full-dose IPV) that was greater than −10 percentage points.

For all three poliovirus serotypes, the lower bound of the 95% confidence interval for the difference in seroconversion rates was above −10 percentage points. The dose-sparing IPV was immunologically non-inferior to full-dose IPV for all three poliovirus serotypes.

In plain terms, non-inferior means that the immune response produced by ds-IPV was not clinically meaningfully worse than that produced by the standard full-dose vaccine, according to the study's predefined non-inferiority margin. The seroconversion rates in the ds-IPV group ranged from 94.7% to 97.3% across the three serotypes.

Safety Findings

Safety evaluation was a pre-specified secondary objective of the trial. Safety assessment included monitoring for immediate adverse events, solicited adverse events (pre-specified local and systemic reactions recorded after each dose), unsolicited adverse events, and serious adverse events.

Solicited local reactions—including tenderness, redness and swelling—and systemic reactions including fever occurred in at least 10% of participants in both vaccine groups. The overall safety profile was similar between the ds-IPV and full-dose IPV groups.

No causally related serious adverse events were reported.

Complete safety data including specific adverse event rates and comparisons between groups are reported in the original peer-reviewed publication.

Clinical and Public Health Significance

A vaccine requiring approximately one-fourth the antigen content of standard full-dose IPV, if confirmed immunogenic and safe, has several potential implications for polio eradication efforts:

• Reducing the per-dose cost of IPV, making it more accessible to national immunisation programmes in lower-income countries
• Extending existing antigen supply further during periods of global IPV shortage
• Simplifying campaign delivery through standard intramuscular administration, rather than the technically demanding intradermal route required for fractional-dose IPV
• Supporting a more consistent IPV supply for populations that have received birth-dose bivalent OPV, as in India's immunisation programme

The publication notes that this study's findings are consistent with an earlier trial by the same investigators that demonstrated non-inferiority of ds-IPV compared with full-dose IPV in infants in Bangladesh, where participants had not received a birth dose of bOPV. The present India-based study was specifically designed to evaluate ds-IPV in the context of a prior bOPV birth dose, which is relevant to countries following India's immunisation schedule.

The vaccine has not been described as already licensed or incorporated into national policy at the time of publication.

Relevance to India's Polio Eradication Strategy

India's achievement of polio-free certification in 2014 was among the most significant public health milestones in the country's history. Maintaining that status requires continued vigilance across several domains:

• Immunity gap management: As birth cohorts accumulate who have never received type 2 OPV following its withdrawal, type 2 immunity must be maintained through IPV
• Vaccine-derived poliovirus surveillance: Circulating vaccine-derived poliovirus strains require active monitoring and response capability
• Import risk: Poliovirus can be imported from countries where it remains endemic, making sustained domestic population immunity essential
• IPV access and coverage: Scaling up IPV coverage within India's Universal Immunisation Programme and ensuring consistent supply is a continuing priority

Research into dose-sparing IPV formulations is therefore directly relevant to India's ongoing strategy. A safe and effective adjuvanted ds-IPV developed and validated in India could contribute to domestic programmes and to global vaccine supply efforts.

Contribution of the Indian Study Centres

This phase 2/3 trial was conducted at nine tertiary care hospitals across India. The trial's authors and their institutional affiliations are listed in the published paper. Named investigators and their affiliations include investigators from Serum Institute of India Pvt. Ltd. (Pune), the National Institute of Cholera and Enteric Diseases (Kolkata), Post Graduate Institute of Medical Education and Research (Chandigarh), and King George Hospital / Andhra Medical College (Visakhapatnam), along with co-investigators at additional institutions listed in the original publication.

Readers should refer to the original article for the complete and verified list of author affiliations and institutional participants.

Role of Andhra Medical College and King George Hospital, Visakhapatnam

King George Hospital, Visakhapatnam — affiliated with Andhra Medical College — was one of the clinical trial sites participating in this multi-centre study. Prof. Bheemisetty Srinivasa Chakravarthy is listed among the publication's authors, identified with affiliation d (King George Hospital, Visakhapatnam, Andhra Pradesh, India) in the original paper, as a co-author and investigator at the King George Hospital study site.

Key Takeaways

Original Publication

This page is an educational summary only. The complete trial data, methods, results, discussion and conclusions are available in the peer-reviewed publication in The Lancet Infectious Diseases. Clinicians, researchers and policymakers should refer to the original article for all clinical and programmatic decision-making.

📄 Read the Original Publication →

References

The following sources informed the contextual sections of this summary. For specific trial data, methods and results, refer directly to the original publication.

1. Kulkarni PS, Desai SA, Kanungo S, Dutta S, Gupta M, Chakravarthy BS, et al. Immunogenicity and safety of a dose-sparing inactivated poliovirus vaccine in infants in India: a phase 2/3, double-blind, randomised controlled trial. The Lancet Infectious Diseases. Published online 15 May 2026. DOI: 10.1016/S1473-3099(26)00108-8. Available at: https://doi.org/10.1016/S1473-3099(26)00108-8
2. World Health Organization. Polio vaccines: WHO position paper — March 2016. Weekly Epidemiological Record. 2016;91(12):145–168.
3. Global Polio Eradication Initiative. Polio eradication strategy 2022–2026: deliver on the promise. Geneva: WHO; 2021.
4. World Health Organization. Meeting of the Strategic Advisory Group of Experts on Immunization, April 2023: conclusions and recommendations. Weekly Epidemiological Record. 2023;98(19):165–196.