The study was designed as a double-blind, randomized, positive-controlled clinical trial. Participants were allocated in a 1:1:1 ratio to receive either the test Sabin strain-based inactivated poliovirus vaccine, developed by the Wuhan Institute of Biological Products, a control inactivated poliovirus vaccine or a control wild-type inactivated poliovirus vaccine. Vaccinations were administered when the infants were two, three and four months old. Blood samples were collected before the first dose and 28 days after the third dose, then tested for neutralizing activity against ten individual poliovirus strains. The immunogenicity analysis used a pre-protocol population comprising the 282 infants who finished all three vaccinations and supplied both pre- and post-immunization samples within the specified time window.

The test vaccine’s seroconversion rates across the ten strains ranged from 91.58% to 100%. The corresponding ranges were 87.23% to 98.94% for the control inactivated vaccine and 94.62% to 100% for the control wild-type vaccine. Geometric mean antibody titers were 40.24 to 2,876.29 for the test vaccine, 25.85 to 1,658.58 for the control inactivated vaccine and 116.2 to 958.12 for the control wild-type vaccine. Against most wild-type strains, the test vaccine’s geometric mean titers were higher than those of the control inactivated vaccine but lower than those induced by the control wild-type vaccine for several strains. These laboratory measurements showed that the test vaccine stimulated antibodies capable of neutralizing the panel of polioviruses included in the assay; they did not directly establish protection against infection, transmission or paralytic disease.

Investigators assessed solicited systemic and local reactions for seven days after each vaccination, unsolicited adverse events for 28 days after each dose and serious adverse events for up to six months after the third vaccination. Fever was the most common solicited systemic reaction, followed by irritation, while injection-site pain was a representative solicited local adverse event in the test-vaccine group. The investigators characterized the safety profiles of all three study groups as acceptable and reported no vaccine-related serious adverse events. The test vaccine nevertheless had a higher incidence of mild-to-moderate adverse reactions than both registered control vaccines, making reactogenicity an important distinction alongside the favorable antibody-response results.

Overall, the findings support the immunogenicity and short-term safety of the test Sabin strain-based inactivated vaccine in the population studied. The authors said its broad cross-neutralization capacity could make it potentially useful in global polio-eradication strategies, particularly for countries transitioning from oral polio vaccine toward affordable schedules based on inactivated vaccine. That conclusion remains a potential application rather than a demonstrated effect of this trial. The study did not measure whether the vaccine prevented poliovirus infection, reduced community transmission or lowered the incidence of paralytic polio, and its findings therefore cannot establish clinical efficacy against those outcomes. The trial was registered as CTR20211257 on 7 June 2021 on the China Drug Clinical Trial Registration and Information Disclosure Platform.

Subject of Research: Immunogenicity and safety of a Sabin strain-based inactivated poliovirus vaccine in infants

Article Title: Safety and cross-neutralization capacity of a Sabin strain-based inactivated polio vaccine: a randomized, double-blind, positive-control clinical trial in 2-month-old infants

Article References: Lu, W., Zhao, L., Zhang, Z., Wu, C., Guo, H., Li, Q., Chen, W., Li, G., Zhao, W., Dong, X., Yu, G., Li, G., & Li, X. (2026). Safety and cross-neutralization capacity of a Sabin strain-based inactivated polio vaccine: a randomized, double-blind, positive-control clinical trial in 2-month-old infants. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14411-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14411-2

Keywords: poliovirus, inactivated polio vaccine, Sabin strain, cross-neutralization, seroconversion, neutralizing antibodies, infant immunization, vaccine safety, polio eradication, Safety, capacity, Sabin

The trial was designed as a prospective, open-label, multicenter, active-controlled study conducted across 31 clinical sites in India, enrolling healthy infants who had never received a pneumococcal conjugate vaccine. Participants aged 6 to 8 weeks at enrollment received three primary doses of either BE-PCV14 or Prevenar 13, followed by a booster dose administered at 12 to 15 months of age, a regimen commonly described as a 3p plus 1 schedule. The investigators, led by Subhash Thuluva of Biological E Limited in Hyderabad, measured serotype-specific immunoglobulin G antibodies against all 14 vaccine serotypes as well as the cross-protective serotype 6A, assessed 28 days after the booster dose. The primary immunological benchmarks were seroresponse rates, defined as the proportion of children achieving serotype-specific IgG concentrations of at least 0.35 micrograms per milliliter, a threshold long used as a correlate of protection against invasive pneumococcal disease, along with geometric mean concentrations of antibody.

The immunogenicity analysis included 559 children who received BE-PCV14 and 147 who received PCV13, providing a substantial evidence base for the comparison. The results were striking in their consistency: after the booster dose, seroresponse rates with BE-PCV14 reached at least 92.8 percent for every one of the 14 vaccine serotypes, and climbed to 96.2 percent for serotype 6A, which is not itself in the vaccine but is known to elicit cross-protection through immunological relatedness to vaccine serotype 6B. For the serotypes shared between the two vaccines, the immune responses elicited by BE-PCV14 were comparable to those generated by Prevenar 13, and post hoc statistical analyses formally demonstrated non-inferiority for all 14 serotypes by both seroresponse and antibody concentration criteria.

The non-inferiority assessment deserves particular attention because of its methodological rigor. The investigators pre-specified that BE-PCV14 would be considered non-inferior to PCV13 for a given serotype if the lower bound of the 95 percent confidence interval for the difference in seroresponse rates exceeded minus 10 percent, and if the lower bound of the confidence interval for the ratio of geometric mean concentrations exceeded 0.5. These are the kinds of thresholds that regulators and vaccine advisory bodies use to judge whether a new product can reasonably substitute for an established one. BE-PCV14 cleared both hurdles for all 14 serotypes, a result that, in the words of the trial team, establishes the vaccine as a credible alternative within existing infant immunization schedules rather than an entirely new paradigm requiring altered dosing strategies.

Perhaps the most consequential finding involves serotypes 22F and 33F, the two additional strains incorporated into BE-PCV14 that are absent from PCV13. The vaccine induced strong antibody responses to both, with booster-induced increases in antibody concentration ranging from 2.4-fold to 5.3-fold across serotypes when compared with pre-booster levels. This matters because pneumococcal serotype replacement is a well-documented phenomenon: when a vaccine eliminates the strains it targets, other strains that were previously less common can expand to fill the ecological vacuum. Serotypes 22F and 33F have been increasingly recognized as causes of invasive pneumococcal disease in countries that have deployed PCV13 at scale, and their inclusion in a new vaccine represents a forward-looking strategy intended to stay ahead of shifting disease epidemiology rather than merely replicate existing coverage.

Safety data from the trial were equally reassuring. Adverse events occurred at similarly low frequencies in both vaccine groups and were predominantly mild local reactions, such as injection-site tenderness or redness, or transient fever. Only two serious adverse events were recorded among BE-PCV14 recipients, and the investigators judged neither to be related to vaccination. The safety profile through 28 days after the booster dose, therefore, mirrors the well-characterized tolerability of licensed pneumococcal conjugate vaccines, an essential consideration for a product intended for universal infant immunization in resource-constrained settings where health systems may have limited capacity to manage vaccine-associated complications.

The trial, registered prospectively with the Clinical Trials Registry of India under identifier CTRI/2023/09/057894 and approved by India’s Central Drugs Standard Control Organisation, was conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines, with written informed consent obtained from the parents or legally authorized representatives of all participants. Ethics committees overseeing each of the 31 participating sites granted approval, including the Institutional Ethics Committee of the All India Institute of Medical Sciences. The study, funded entirely by Biological E Limited, carries the inherent limitation that many of the authors are or were employees of the sponsoring company, though the trial’s active-controlled design against a licensed comparator and its prespecified statistical criteria provide meaningful safeguards against bias in the immunogenicity conclusions.

The public health significance of this work extends well beyond India’s borders. Streptococcus pneumoniae is responsible for hundreds of thousands of deaths among children under five each year, with the overwhelming majority occurring in low- and middle-income countries where access to effective vaccines has historically lagged behind wealthy nations. Pneumococcal conjugate vaccines have traditionally been among the most expensive components of childhood immunization schedules, and the introduction of a WHO-prequalified vaccine manufactured in a middle-income country carries the potential to lower prices, expand supply, and reduce dependence on a small number of multinational manufacturers. For India, which runs one of the largest immunization programs in the world through its Universal Immunization Programme, a domestically produced 14-valent vaccine that slots into the standard 3-plus-1 schedule offers both strategic and epidemiological advantages.

The trial’s findings also speak to a broader evolution in pneumococcal vaccine science. The 0.35 micrograms per milliliter IgG threshold used in this study is a population-level benchmark derived from efficacy trials of earlier conjugate vaccines, and while it does not guarantee individual protection, it remains the standard immunological bridge for licensure and comparison of new formulations. The demonstrated booster response, with antibody concentrations rising severalfold after the toddler dose, indicates that BE-PCV14 successfully exploits the immunological memory established during the primary series, an attribute that underpins the durability of protection in the second year of life, when the burden of invasive pneumococcal disease and pneumonia peaks in unvaccinated populations.

As pneumococcal disease patterns continue to shift under the selective pressure of global vaccination, the arrival of a well-tolerated, immunogenic 14-valent conjugate vaccine that extends coverage to emerging serotypes while matching the performance of the established 13-valent standard represents a meaningful advance. The authors conclude that PNEUBEVAX 14, when used as a booster in a 3-plus-1 schedule, is well tolerated and elicits robust responses comparable to PCV13 for shared serotypes while effectively broadening coverage to 15 serotypes when cross-protection against 6A is counted. For immunization programs weighing how to future-proof their pneumococcal strategies, this trial provides a substantial and encouraging body of evidence that broader serotype coverage need not come at the cost of safety or immunogenicity.

Subject of Research: Safety and immunogenicity of a 14-valent pneumococcal conjugate vaccine in Indian infants and toddlers

Article Title: Safety and immunogenicity of a 14-valent pneumococcal conjugate vaccine (BE-PCV14) administered in a 3p + 1 schedule to healthy Indian infants and toddlers: a prospective, multicenter, active-controlled phase IV trial

Article References: Thuluva, S., Gunneri, S., Ningaiah, S., Yerroju, V., Mogulla, R. R., Dhar, C., Thammireddy, K., Desai, S., Paliwal, P., Loka, C., Esanakarra, R., Narayandas, S., Chakravarthy, B. S., Narayan, J. P., Mahantshetti, N. S., Narang, M., Karayar, R. A., Verma, S., Thakkar, P. A., & Prabhakar, J. P. (2026). Safety and immunogenicity of a 14-valent pneumococcal conjugate vaccine (BE-PCV14) administered in a 3p + 1 schedule to healthy Indian infants and toddlers: a prospective, multicenter, active-controlled phase IV trial. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14412-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14412-1

Keywords: pneumococcal conjugate vaccine, PNEUBEVAX 14, BE-PCV14, PCV13, infant immunization, serotype 22F, serotype 33F, invasive pneumococcal disease, India, phase IV trial, booster vaccination, Streptococcus pneumoniae