Immunogenicity and protective efficacy of monovalent PCVs containing 22F and 33F polysaccharides in mouse models of colonization and co-infection

Abstract

BackgroundIn the current transmission, we studied the immunogenicity and protective efficacy of serotypes 22F and 33F in the prevention of colonization and of invasive Streptococcus pneumoniae (Spn) pathogenesis during an influenza co-infection. Serotypes 22F and 33F are emerging Spn serotypes, which are not part of currently administered pneumococcal conjugate vaccine formulations (PCVs). Spn serotype 6A is an ingredient in the currently administered PCV13 vaccine and was therefore included in the study as a control. MethodsAdult (six weeks) and infant (two weeks) C57BL/6 mice were intranasally infected in the nasopharynx (NP) with Spn serotypes 22F, 33F, or 6A. Influenza A H1N1 A/Puerto Rico/8/193 virus (PR8) was introduced one day after the NP Spn colonization. In an immunization challenge study, mice were vaccinated with monovalent 22F, 33F, or 6A polysaccharide conjugated to the CRM197 antigen. The immunized mice were colonized or co-infected to study the vaccines efficacy. ResultsAll three Spn serotypes established colonization in adult and infant mice. The co-infected mice showed an increase in Spn NP density. Invasive Spn infection (bacteremia) was observed following the co-infection with serotypes 22F and 6A but not 33F in adult mice, whereas infant mice developed bacteremia following co-infection with all three Spn serotypes. The vaccinations led to robust serum antibody responses to capsular polysaccharides 22F, 6A, and less for 33F. The vaccinations resulted in reductions of Spn NP colonization density for all three serotypes, prevention of bacteremia, and increased survival with Spn serotypes 22F and 6A. Passive transfer of antisera was associated with a reduction of Spn colonization densities in infant mice. ConclusionVaccinations with monovalent 22F, 33F, or 6A formulations protect against Spn colonization, and the efficacy of the 22F vaccination was comparable to the 6A vaccination in preventing an invasive Spn bacterial infection during an influenza co-infection.