Formulation of a killed whole cell pneumococcus vaccine - effect of aluminum adjuvants on the antibody and IL-17 response

Stanley L Hem,Harm Hogenesch,Kathleen Anderson,Bethany Hansen,Anisa Dunham,Jean-Francois Maisonneuve

doi:10.1186/1476-8518-9-5

Stanley L Hem, Harm Hogenesch + Show 4 more

Open Access

https://doi.org/10.1186/1476-8518-9-5

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Abstract

BackgroundStreptococcus pneumoniae causes widespread morbidity and mortality. Current vaccines contain free polysaccharides or protein-polysaccharide conjugates, and do not induce protection against serotypes that are not included in the vaccines. An affordable and broadly protective vaccine is very desirable. The goal of this study was to determine the optimal formulation of a killed whole cell pneumococcal vaccine with aluminum-containing adjuvants for intramuscular injection.MethodsFour aluminium-containing adjuvants were prepared with different levels of surface phosphate groups resulting in different adsorptive capacities and affinities for the vaccine antigens. Mice were immunized three times and the antigen-specific antibody titers and IL-17 responses in blood were analyzed.ResultsAlthough all adjuvants induced significantly higher antibody titers than antigen without adjuvant, the vaccine containing aluminum phosphate adjuvant (AP) produced the highest antibody response when low doses of antigen were used. Aluminum hydroxide adjuvant (AH) induced an equal or better antibody response at high doses compared with AP. Vaccines formulated with AH, but not with AP, induced an IL-17 response. The vaccine formulated with AH was stable and retained full immunogenicity when stored at 4°C for 4 months.ConclusionsAntibodies are important for protection against systemic streptococcal disease and IL-17 is critical in the prevention of nasopharyngeal colonization by S. pneumoniae in the mouse model. The formulation of the whole killed bacterial cells with AH resulted in a stable vaccine that induced both antibodies and an IL-17 response. These experiments underscore the importance of formulation studies with aluminium containing adjuvants for the development of stable and effective vaccines.

Highlights

Streptococcus pneumoniae causes widespread morbidity and mortality
There was no detectable adsorption of protein to phosphate treated AP (PTAP)
The bacteria were associated with the aluminum hydroxide (AH) and aluminum phosphate (AP) aggregates and were not observed in the liquid phase separating the adjuvant aggregates

Summary

Introduction

Current vaccines contain free polysaccharides or protein-polysaccharide conjugates, and do not induce protection against serotypes that are not included in the vaccines. Streptococcus pneumoniae (pneumococcus) is a Grampositive, encapsulated diplococcus that is commonly present as a commensal bacterium in the microbial flora of the upper respiratory tract without causing clinical disease These bacteria cause great morbidity and mortality throughout the world. The conjugated vaccines that are T-dependent induce a good immune response in young children and infants These vaccines have greatly reduced disease caused by the pneumococcal serotypes included in the vaccines in countries where these vaccines are widely used. Increased prevalence of non-vaccine serotypes has been observed following the implementation of pneumococcus vaccination programs [4,5] These considerations have led to the pursuit of alternative vaccination strategies, including the use of protein antigens that are shared among the different serotypes. A potentially successful approach is the use of killed, non-encapsulated pneumococci (whole cell antigen - WCA) which provides multiple common antigens for inducing an immune response that is protective across the different serotypes, and is relatively inexpensive to prepare [6]

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