An investigational pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine (PCV13) was well-tolerated and immunogenic but did not show incremental efficacy in preventing acute otitis media (AOM) or acute lower respiratory tract infection in children, according to research results published in Vaccine.

In this phase 2b trial (ClinicalTrials.gov identifier: NCT01545375), researchers assessed vaccine effectiveness against AOM and acute lower respiratory tract infection induced by an investigational pneumococcal protein-based vaccine containing 10 µg each of pneumolysin toxoid and pneumococcal histidine triad protein D. Researchers included 1803 Native American infants living in the southwestern United States, in and around the Navajo and White Mountain Apache reservations. Infants aged 6 to 12 weeks were randomly assigned in a 1:1 ratio to receive either the investigational vaccine or placebo at ages 2, 4, 6, and 12 to 15 months, each co-administered with PCV13. Researchers also reported immunogenicity of the protein antigens and safety of the investigational vaccine in a subcohort of participants.

Of the 1803 infants included in the study, 900 were in the investigational group (investigational vaccine + PCV13) and 903 were in the control group (placebo + PCV13). The subcohort analysis included 808 infants in the investigational group and 831 in the control group.

In the subcohort analysis, incremental efficacy of the investigational vaccine in preventing AOM as defined by the American Academy of Pediatrics over PCV13 was not demonstrated. Vaccine efficacy against all episodes of AOM was 3.8% (95% CI, -11.4 to 16.9). Vaccine efficacy against the first AOM episode was 11.3% (95% CI, -3.4, 23.9). Point estimates of vaccine efficacy against other AOM outcomes ranged between 2.9% (95% CI, -9.5 to 14.0) and 5.2% (95% CI, -8.0 to 16.8). Point estimates of vaccine efficacy against acute lower respiratory tract infection outcomes ranged between -4.4% (95% CI, -39.2 to 21.8) and 2.0% (95% CI, -18.3 to 18.8). Vaccine efficacy tended to be higher against first AOM and ALRI compared with subsequent episodes.

In spite of the lack of demonstrated efficacy, researchers observed a robust serum antibody response to the protein antigens. Antibody levels to the pneumolysin component were substantially higher in the investigational group compared with the control group at all time points, while antibody levels to the pneumococcal histidine triad protein were within the same range for both groups. In addition, the effect of seasonal influenza vaccination in a post-hoc exploratory analysis did not show a consistent effect of the influenza vaccination on the vaccine efficacy of the investigational vaccine again AOM and acute lower respiratory tract infection.

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Pain and irritability were the most frequently reported solicited local and general symptoms, respectively, after primary and booster vaccination. The frequency of solicited and unsolicited adverse events was similar in both groups after primary and booster vaccination.

“The interactions between immunity, carriage, and progression to disease are complex and poorly understood,” noted the researchers. “Future studies should aim to improve our understanding of the effect of anti-protein antibodies on pathogenesis of pneumococcal disease,” they concluded.

Disclosure: This study was funded by GlaxoSmithKline Biologicals SA. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Hammitt LL, Campbell JC, Borys D, et al. Efficacy, safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: a phase IIb randomized study [published online October 16, 2019]. Vaccine. doi:10.1016/j.vaccine.2019.09.076