Dose-Sparing Polio Vaccine Matches Full-Dose Immunogenicity and Safety in Infants

Advancing Polio Eradication: Strategies for Sustainable Vaccine Supply

Global efforts to eradicate poliomyelitis rely heavily on effective vaccination strategies, primarily utilizing oral poliovirus vaccine (OPV) and inactivated poliovirus vaccine (IPV). While OPV provides robust mucosal immunity, its live attenuated nature carries a risk of vaccine-derived polioviruses, necessitating a shift towards IPV-centric immunization schedules [1, 2]. However, the widespread adoption of IPV faces hurdles, including its procurement cost and the logistical challenges of ensuring consistent supply for large-scale campaigns [3]. These factors underscore the ongoing need for innovative vaccine formulations that can maintain strong immunogenicity and safety while optimizing resource utilization [4, 5]. Such advancements are crucial for sustaining high population immunity and preventing outbreaks as the world approaches the final stages of polio eradication [6]. A new study now offers fresh insights into a potential solution to these challenges.

Addressing Supply Challenges with a Dose-Sparing IPV

The development of new vaccine formulations is particularly relevant given existing challenges in global polio eradication efforts. Currently, several countries are employing fractionated or limited-dose regimens of full-dose inactivated poliovirus vaccine (IPV) in infants, often in conjunction with oral poliovirus vaccine (OPV). This strategy is primarily driven by two critical factors: the procurement cost of IPV and the delivery challenges associated with its use in large-scale vaccination campaigns. These logistical and economic pressures highlight the need for more resource-efficient IPV options that do not compromise immunogenicity or safety.

In response to these demands, an adjuvanted dose-sparing IPV (ds-IPV) was developed in India. This innovative formulation contains approximately one-fourth the antigen content of the standard full-dose IPV, aiming to extend vaccine supply without diminishing protective immunity. To rigorously evaluate this new vaccine, the researchers conducted a non-inferiority trial specifically designed to compare the immune response of this ds-IPV with that of standard IPV in infants, providing a direct assessment of its potential as a viable alternative.

Trial Design and Participant Characteristics

The evaluation of the dose-sparing inactivated poliovirus vaccine (ds-IPV) was conducted through a phase 2/3, double-blind, randomised controlled trial across nine tertiary care hospitals in India. The study enrolled healthy infants aged 6-8 weeks who had previously received a birth dose of bivalent oral poliovirus vaccine (OPV). To ensure a focused assessment of the ds-IPV, participants were excluded if they presented with fever or acute infection, or if they had a history of receiving or planned to receive any other poliovirus-containing vaccines. Infants were randomly assigned in a 1:1 ratio to receive either ds-IPV or standard IPV, with block randomisation managed via an interactive web response system. The vaccine regimen consisted of three 0.5 mL doses administered intramuscularly at 6 weeks, 10 weeks, and 14 weeks of age. To maintain blinding, vaccine syringes were masked with an opaque peel prior to administration, and the site staff evaluating outcomes, participants' parents, and laboratory personnel were all masked to the vaccine allocations. Importantly, all participants also received other routine infant immunizations concomitantly, including oral rotavirus vaccine, and injectable DTwP-HB-Hib and pneumococcal conjugate vaccine, administered in the contralateral thigh by the intramuscular route.

To assess immune response, blood samples were collected at baseline, before the first vaccine dose, and again at 28 days after the third dose. Neutralizing antibodies against each poliovirus serotype were then measured using a microneutralization assay. The primary outcome for the study was the type-specific percentage seroconversion at 28 days after the third dose of either ds-IPV or IPV, with a non-inferiority margin of ≥10%. Secondary outcomes included type-specific geometric mean titres and percentage seroprotection, defined as a titre ≥8. These outcomes were primarily assessed in the per-protocol population, with the full analysis population serving as a supportive cohort. Safety evaluation, a key secondary outcome, encompassed immediate, solicited, unsolicited, and serious adverse events. The study, registered with the Clinical Trials Registry of India (CTRI/2022/05/042363), was conducted between May 23, 2022, and April 13, 2024. Out of 658 participants screened, 648 were deemed eligible and randomly assigned to either the ds-IPV group (n=324) or the IPV group (n=324). Following randomisation, consent was withdrawn for five participants, resulting in a total of 643 infants receiving vaccine, specifically 323 in the ds-IPV group and 320 in the IPV group.

Immunogenicity Outcomes: Seroconversion Rates

The study's primary outcome focused on type-specific seroconversion rates, which indicate the development of protective antibodies following vaccination. For type 1 poliovirus, the seroconversion rate in the dose-sparing inactivated poliovirus vaccine (ds-IPV) group was 283 (94.7% [95% CI 91.5 to 96.9]) of 299 participants. In comparison, the standard inactivated poliovirus vaccine (IPV) group demonstrated a seroconversion rate of 270 (92.8% [89.2 to 95.5]) of 291 participants for type 1 poliovirus. The observed difference in seroconversion rates between the ds-IPV and IPV groups for type 1 poliovirus was 1.9 (95% CI -2.1 to 5.8), indicating a comparable immune response.

Similar findings were observed for the other poliovirus serotypes. For type 2 poliovirus, the ds-IPV group achieved a seroconversion rate of 287 (96.3% [93.5 to 98.1]) of 298 participants, while the IPV group showed a rate of 284 (97.9% [95.6 to 99.2]) of 290 participants. The difference in seroconversion rates for type 2 poliovirus was -1.6 (95% CI -4.7 to 1.5). Regarding type 3 poliovirus, the ds-IPV group had a seroconversion rate of 291 (97.3% [94.8 to 98.8]) of 299 participants, closely matching the IPV group's rate of 288 (99.0% [97.0 to 99.8]) of 291 participants. The difference in seroconversion rates for type 3 poliovirus was -1.6 (95% CI -3.8 to 0.5). These data collectively support the immunological non-inferiority of the ds-IPV compared to standard IPV across all three poliovirus serotypes, suggesting it elicits a robust and equivalent antibody response.

Safety Profile and Clinical Implications

Beyond immunogenicity, the study meticulously evaluated the safety profile of the dose-sparing inactivated poliovirus vaccine (ds-IPV). The researchers reported that solicited events, including tenderness, redness, swelling, and fever, were very common (≥10%) in both vaccine groups, meaning these local and systemic reactions occurred frequently in infants receiving either ds-IPV or standard inactivated poliovirus vaccine (IPV). Crucially, the trial found no causally related serious adverse events in either group, indicating a favorable safety profile for both vaccine formulations. These safety findings, combined with the immunogenicity data, led the researchers to conclude that ds-IPV was immunologically non-inferior to IPV and exhibited a similar safety profile to the standard vaccine.

The clinical implications of these findings are substantial. The data suggest that the new adjuvanted IPV could become an alternative option to IPV, offering a viable substitute for current standard formulations. This is particularly relevant for global polio eradication efforts, as the availability of ds-IPV will support a constant supply of IPV for use in poliovirus-naive and exposed target populations. This addresses critical challenges related to vaccine procurement costs and delivery logistics, especially in regions with high demand or supply chain vulnerabilities. The study was funded by the Serum Institute of India, the developer of the ds-IPV, underscoring the commitment to expanding access to polio vaccination.

References

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2. Hird TR, Grassly NC. Systematic Review of Mucosal Immunity Induced by Oral and Inactivated Poliovirus Vaccines against Virus Shedding following Oral Poliovirus Challenge. PLoS Pathogens. 2012. doi:10.1371/journal.ppat.1002599

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