Humoral responses to oxidized low-density lipoprotein and related bacterial antigens after pneumococcal vaccine.

Antibodies to oxidized low-density lipoprotein (oxLDL) may modulate the development of atherosclerosis. Antibodies to oxLDL may also react with cell wall polysaccharides (CWPS) of Streptococcus pneumoniae because both antigens share a common phosphorylcholine moiety. In hypercholesteremic mice, immunization with pneumococcal organisms elicited antibodies to oxLDL and protection against atherosclerosis. In humans, we determined whether the widely used adult pneumococcal polysaccharide vaccine augmented antibodies to oxLDL, CWPS, and phosphorylcholine, providing the potential to retard atherogenesis. Before and 4 weeks after pneumococcal vaccination of 23 healthy adults (11 smokers and 12 matched nonsmokers), we characterized IgG, IgM, and IgA to pneumococcal capsular polysaccharides, CWPS, and phosphorylcholine, IgG and IgM to oxLDL, and fasting serum lipids. The pneumococcal vaccine elicited significant increases in each antibody class to surface capsular polysaccharides. In contrast, only IgG to CWPS increased modestly and only among smokers. Moreover, antibodies to neither phosphorylcholine nor oxLDL increased consistently in either group. The pneumococcal polysaccharide vaccine effectively elicits antibodies to the bacterial capsule. The vaccine had no effect on serum lipids. The vaccine did not augment antibodies to CWPS, to its component phosphorylcholine, or to oxLDL, which are antibodies that have been proposed to modify the uptake of oxLDL by macrophages and the pathogenesis of atherosclerosis.

Inhibition of HIV-1 infectivity and epithelial cell transfer by human monoclonal IgG and IgA antibodies carrying the b12 V region.

Both IgG and secretory IgA Abs in mucosal secretions have been implicated in blocking the earliest events in HIV-1 transit across epithelial barriers, although the mechanisms by which this occurs remain largely unknown. In this study, we report the production and characterization of a human rIgA(2) mAb that carries the V regions of IgG1 b12, a potent and broadly neutralizing anti-gp120 Ab which has been shown to protect macaques against vaginal simian/HIV challenge. Monomeric, dimeric, polymeric, and secretory IgA(2) derivatives of b12 reacted with gp120 and neutralized CCR5- and CXCR4-tropic strains of HIV-1 in vitro. With respect to the protective effects of these Abs at mucosal surfaces, we demonstrated that IgG1 b12 and IgA(2) b12 inhibited the transfer of cell-free HIV-1 from ME-180 cells, a human cervical epithelial cell line, as well as Caco-2 cells, a human colonic epithelial cell line, to human PBMCs. Inhibition of viral transfer was due to the ability of b12 to block both viral attachment to and uptake by epithelial cells. These data demonstrate that IgG and IgA MAbs directed against a highly conserved epitope on gp120 can interfere with the earliest steps in HIV-1 transmission across mucosal surfaces, and reveal a possible mechanism by which b12 protects the vaginal mucosal against viral challenge in vivo.