{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T14:06:53Z","timestamp":1779458813354,"version":"3.53.1"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biological E. Limited"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Pneumococcal conjugate vaccines (PCVs) have substantially reduced pneumococcal disease in children; however, serotype distribution varies geographically, and residual disease due to non-PCV13 serotypes persists. Biological E\u2019s PNEUBEVAX 14\u00ae (BE-PCV14), a WHO-prequalified 14-valent PCV, expands coverage by including serotypes 22F and 33F. As PCVs are co-administered with routine Expanded Programme on Immunization (EPI) vaccines, post-licensure data on safety, co-administration, and lot-to-lot consistency are essential. This multicenter phase IV study evaluated BE-PCV14 in healthy PCV-na\u00efve infants aged 6\u20138 weeks across 31 sites in India. Methods: A total of 2600 infants were enrolled and vaccinated at 6, 10, and 14 weeks of age; 2300 received BE-PCV14 and 300 received PCV13. All participants received concomitant DTwP-HepB-IPV-Hib and oral rotavirus vaccines per routine schedule. Safety was assessed through solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). Immunogenicity subsets evaluated responses to co-administered vaccines and serotype-specific responses across three BE-PCV14 lots. Results: Among 2600 vaccinated infants, at least one AE occurred in 26.35% (95% CI: 24.59, 28.19) of BE-PCV14 and 24.67% (95% CI: 20.13, 29.84) of PCV13 recipients; most were mild. Injection-site pain and pyrexia were the most common events. Immune responses to co-administered vaccines were comparable between groups and met the non-inferiority criteria: lower bound of the two-sided 95% CI &gt; \u221210 percentage points for seroprotection\/seroconversion rate differences using the Farrington\u2013Manning method. Lot-to-lot consistency was demonstrated, with all GMC ratios within the predefined equivalence margin (0.5\u20132.0). Conclusions: BE-PCV14 was well tolerated. Immune responses to co-administered routine EPI vaccines met predefined non-inferiority criteria, supporting the interpretation that BE-PCV14 did not result in clinically meaningful immune interference. Consistent immune responses across manufacturing lots further support its use in infant immunization programs.<\/jats:p>","DOI":"10.3390\/vaccines14060464","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Immunogenicity of Co-Administered Vaccines, and Lot-to-Lot Consistency of a 14-Valent Pneumococcal Conjugate Vaccine (PNEUBEVAX 14\u00ae) Administered at 6\u201310\u201314 Weeks in Healthy Infants: A Multicenter, Phase IV Trial"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-420X","authenticated-orcid":false,"given":"Subhash","family":"Thuluva","sequence":"first","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subbareddy","family":"Gunneri","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6116-4959","authenticated-orcid":false,"given":"Siddalingaiah","family":"Ningaiah","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Yerroju","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-7701","authenticated-orcid":false,"given":"Rammohan Reddy","family":"Mogulla","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7614-4026","authenticated-orcid":false,"given":"Kamal","family":"Thammireddy","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag","family":"Dhar","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6069-7354","authenticated-orcid":false,"given":"Shivani","family":"Desai","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Paliwal","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrudu","family":"Loka","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaganesh","family":"Balne","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Kommanapalli","sequence":"additional","affiliation":[{"name":"Clinical Development, Biological E. Limited, 18\/1&3, Azamabad, Hyderabad 500020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmayi","family":"Joshi","sequence":"additional","affiliation":[{"name":"Belagavi Institute of Medical Sciences, Belgaum 590001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishori Sharan","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Chirayu Hospital, Jaipur 302044, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish P.","family":"Charde","sequence":"additional","affiliation":[{"name":"Gillurkar Multispeciality Hospital, Nagpur 440024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Narang","sequence":"additional","affiliation":[{"name":"Guru Teg Bahadur  Hospital, North East, Delhi 110095, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai Prakash","family":"Narayan","sequence":"additional","affiliation":[{"name":"Jawahar Lal Nehru Medical College, Ajmer 305001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bheemisetty S.","family":"Chakravarthy","sequence":"additional","affiliation":[{"name":"King George Hospital, Visakhapatnam 530002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjana S.","family":"Mahantshetti","sequence":"additional","affiliation":[{"name":"Karnatak Lingayat Education Society Dr. Prabhakar Kore Hospital & Medical Research Centre, Belgaum 590010, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod Prabhakar","family":"Jog","sequence":"additional","affiliation":[{"name":"Medipoint Hospital, Pune 411007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth Madapura","family":"Virupakshappa","sequence":"additional","affiliation":[{"name":"Medstar Speciality Hospital, Bangalore 560092, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savita","family":"Verma","sequence":"additional","affiliation":[{"name":"Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhukar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Shubham Sadbhawana Superspeciality Hospital, Varanasi 221005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pareshkumar A.","family":"Thakkar","sequence":"additional","affiliation":[{"name":"Sir Sayajirao General Hospital, Vadodara 390001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). Pneumococcal conjugate vaccines in infants and children aged <5 years: WHO position paper, September 2025. Wkly. Epidemiol. Rec., 100, 411\u2013437."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e744","DOI":"10.1016\/S2214-109X(18)30247-X","article-title":"Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: Global, regional, and national estimates for 2000\u201315","volume":"6","author":"Wahl","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S1473-3099(24)00665-0","article-title":"Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): A global surveillance analysis","volume":"25","author":"Bennett","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Izurieta, P., Abdel Ghany, M., and Borys, D. (2025). Serotype distribution of invasive and non-invasive pneumococcal disease in children \u22645 years of age following the introduction of 10- and 13-valent pneumococcal conjugate vaccines in infant national immunization programs: A systematic literature review. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1544359"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Balsells, E., Guillot, L., Nair, H., and Kyaw, M.H. (2017). Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177113"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1473-3099(24)00588-7","article-title":"Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): A global surveillance analysis","volume":"25","author":"Quesada","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1016\/j.vaccine.2021.02.026","article-title":"Invasive pneumococcal disease due to 22F and 33F in England: A tail of two serotypes","volume":"39","author":"Groves","year":"2021","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"M\u00e9roc, E., Fletcher, M.A., Hanquet, G., Slack, M.P.E., Baay, M., Hayford, K., Gessner, B.D., and Grant, L.R. (2023). Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine. Microorganisms, 11, Erratum in: Microorganisms\u00a02025, 13, 793. https:\/\/doi.org\/10.3390\/microorganisms13040793.","DOI":"10.3390\/microorganisms13040793"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.vaccine.2022.12.054","article-title":"A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED)","volume":"41","author":"Lupinacci","year":"2023","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1016\/j.vaccine.2024.03.056","article-title":"Immunogenicity and safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14\u2122) administered to 6\u20138 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study","volume":"42","author":"Matur","year":"2024","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jaiswal, N., Singh, M., Das, R.R., Jindal, I., Agarwal, A., Thumburu, K.K., Kumar, A., and Chauhan, A. (2014). Distribution of serotypes, vaccine coverage, and antimicrobial susceptibility pattern of Streptococcus pneumoniae in children living in SAARC countries: A systematic review. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108617"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1007\/s13312-018-1398-x","article-title":"Non-vaccine Pneumococcal Serotypes Among Children with Invasive Pneumococcal Disease","volume":"55","author":"John","year":"2018","journal-title":"Indian Pediatr."},{"key":"ref_13","unstructured":"(2021). National Operational Guidelines on Introduction of Pneumococcal Conjugate Vaccine (PCV), Ministry of Health and Family Welfare, Government of India."},{"key":"ref_14","unstructured":"World Health Organization (2013). Recommendations to Assure the Quality, Safety and Efficacy of Pneumococcal Conjugate Vaccines, World Health Organization. Annex 3, WHO Technical Report Series No. 977."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1001\/jama.2013.228052","article-title":"Immunogenicity of 13-valent pneumococcal conjugate vaccine administered according to 4 different primary immunization schedules in infants: A randomized clinical trial","volume":"310","author":"Spijkerman","year":"2013","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"A Jones, S., Groome, M., Koen, A., Van Niekerk, N., Sewraj, P., Kuwanda, L., Izu, A., Adrian, P.V., and A Madhi, S. (2013). Immunogenicity of seven-valent pneumococcal conjugate vaccine administered at 6, 14 and 40 weeks of age in South African infants. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072794"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Thuluva, S., Matur, R.V., Gunneri, S., Mogulla, R.R., Thammireddy, K., Peta, K.K., Paliwal, P., Mahantshetti, N.S., Banala, R.K., and Siddaiah, P. (2025). Immunogenicity and safety of a multi-human dose formulation of Biological E\u2019s 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14\u00ae) administered to 6-8-week-old healthy infants: A phase 3, single-blind, randomized, active-controlled study. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1550227"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100746","DOI":"10.1016\/j.lansea.2026.100746","article-title":"Immunogenicity and safety of Biological E\u2019s 14-valent pneumococcal conjugate vaccine (PNEUBEVAX 14\u00ae) administered in a 2p + 1 schedule to healthy infants: A multicenter, randomized, active controlled, single-blind, phase III trial","volume":"46","author":"Thuluva","year":"2026","journal-title":"Lancet Reg. Health Southeast Asia"},{"key":"ref_19","unstructured":"World Health Organization PNEUBEVAX 14\u00ae. World Health Organization. Available online: https:\/\/extranet.who.int\/prequal\/vaccines\/p\/pneubevax-14r."},{"key":"ref_20","first-page":"514","article-title":"Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides","volume":"10","author":"Wernette","year":"2003","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Thuluva, S., Matur, R.V., Gunneri, S., Ningaiah, S., Yerroju, V., Mogulla, R.R., Dhara, C., Thammireddya, K., Paliwala, P., and Kawade, A. (2025). Safety and immunogenicity of Biological E\u2019s 14-valent pneumococcal conjugate vaccine (PNEUBEVAX 14\u00ae) administered in a 3p+1 schedule to healthy Indian infants and toddlers: A prospective, multicenter, active-controlled phase IV trial. medRxiv.","DOI":"10.64898\/2025.12.18.25342547"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127916","DOI":"10.1016\/j.vaccine.2025.127916","article-title":"Immunogenicity and safety of concomitant vaccines given with 20-valent pneumococcal conjugate vaccine in healthy infants","volume":"68","author":"Senders","year":"2025","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1097\/INF.0b013e3182906499","article-title":"Immunogenicity, safety and tolerability of 3 lots of 13-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in the United States","volume":"32","author":"Payton","year":"2013","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1473-3099(20)30735-0","article-title":"Immunogenicity and safety of a novel ten-valent pneumococcal conjugate vaccine in healthy infants in The Gambia: A phase 3, randomised, double-blind, non-inferiority trial","volume":"21","author":"Clarke","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","unstructured":"European Medicines Agency (2024). Assessment Report: Prevenar 20. Procedure No. EMEA\/H\/C\/005451\/II\/0012. European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/variation-report\/prevenar-20-previously-apexxnar-h-c-005451-ii-0012-epar-assessment-report-variation_en.pdf."},{"key":"ref_26","unstructured":"(2022). VAXNEUVANCE (Pneumococcal 15-Valent Conjugate Vaccine): BLA Clinical Review Memorandum (Standard No. STN 125741\/6). Available online: https:\/\/www.fda.gov\/media\/160171\/download."},{"key":"ref_27","first-page":"165152","article-title":"Incidence, Pattern, and Severity of Acute Respiratory Infections among Infants and Toddlers of a Peri-Urban Area of Delhi: A 12-Month Prospective Study","volume":"2014","author":"Walke","year":"2014","journal-title":"Int. Sch. Res. Not."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s13312-016-0892-2","article-title":"Rotavirus and other diarrheal disease in a birth cohort from Southern Indian community","volume":"53","author":"Sarkar","year":"2016","journal-title":"Indian Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2023065218","DOI":"10.1542\/peds.2023-065218","article-title":"Safety of a 4-Dose 20-Valent Pneumococcal Conjugate Vaccine Series in Infants: A Randomized Trial","volume":"154","author":"Hajdu","year":"2024","journal-title":"Pediatrics"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/6\/464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:27:02Z","timestamp":1779456422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/6\/464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":29,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["vaccines14060464"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14060464","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}