The Effect of a 13-Valent Conjugate Pneumococcal Vaccine on Circulating Antibodies Against Oxidized LDL and Phosphorylcholine in Man, A Randomized Placebo-Controlled Clinical Trial

SIMPLE SUMMARY: Atherosclerosis is the main underlying mechanism for cardiovascular disease. The main cause for atherosclerosis development is oxidized low density lipoprotein (oxLDL) accumulation in the vessel wall and a subsequent immune response. It has been established that immunoglobulin M antibodies against oxLDL help protect against atherosclerosis. It has been found in mice that vaccination with Streptococcus pneumoniae results in an increase of these protective antibodies and thereby decreases the development of atherosclerosis. In this study, we investigated if this increase of antibodies can be found in human as well. Twenty-four healthy male volunteers were vaccinated with Prevenar-13, a pneumococcal vaccine, using different dosing regimens. An increase in anti-Prevenar antibodies was found, showing that the vaccination worked. However, no increase in protective anti-phosphorylcholine or anti-oxLDL antibodies was observed. This work shows that vaccination against pneumococcal does not seem to be a suitable treatment option to help prevent atherosclerosis development, although further research would be required to test alternative pneumococcal-based vaccines, vaccination regimens or study populations. ABSTRACT: In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae) and anti-oxLDL IgM. In this study we investigated the human translation of this molecular mimicry by vaccination against S. pneumoniae using the Prevenar-13 vaccine. Twenty-four healthy male volunteers were vaccinated with Prevenar-13, either three times, twice or once in a double-blind, placebo-controlled, randomized single center clinical study. Anti-pneumococcal wall, oxLDL and phosphorycholine antibody levels were measured at a fixed serum dilution, as well as circulating lipid levels over the course of 68 weeks. A significant increase in anti-oxLDL IgG and IgM was seen in the group receiving two doses six months apart compared to the placebo. However, these differences were not observed in the groups receiving a single dose, two doses one month apart, or three doses. This study shows that vaccination with Prevenar-13 does not result in robust anti-oxLDL IgM levels in humans. Further research would be required to test alternative pneumococcal-based vaccines, vaccination regimens or study populations, such as cardiovascular disease patients.