• Laura L Hammitt, James C Campbell, Dorota Borys, Robert C Weatherholtz, Raymond Reid, Novalene Goklish, Lawrence H Moulton, Magali Traskine, Yue Song, Kristien Swinnen, Mathuram Santosham, and Katherine L O'Brien.
• Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: LHammitt@JHU.edu.
• Vaccine. 2019 Dec 3; 37 (51): 7482-7492.

BackgroundNative American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs.MethodsIn this phase IIb, double-blind, controlled trial, 6-12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12-15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children.Results1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: -11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (-9.5, 14.0) and 5.2% (-8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between -4.4% (-39.2, 21.8) and 2.0% (-18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants.ConclusionsThe dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated.Clinical Trials RegistrationNCT01545375 (www.clinicaltrials.gov).Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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