Immunogenicity of a Whole-Cell Pertussis Vaccine with Low Lipopolysaccharide Content in Infants

Abstract

ABSTRACT The lack of a clear correlation between the levels of antibody to pertussis antigens and protection against disease lends credence to the possibility that cell-mediated immunity provides primary protection against disease. This phase I comparative trial had the aim of comparing the in vitro cellular immune response and anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) titers induced by a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wP low vaccine) with those induced by the conventional whole-cell pertussis (wP) vaccine. A total of 234 infants were vaccinated at 2, 4, and 6 months with the conventional wP vaccine or the wP low vaccine. Proliferation of CD3 + T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cell culture with stimulation with heat-killed Bordetella pertussis or phytohemagglutinin (PHA). CD3 + , CD4 + , CD8 + , and T-cell receptor γδ-positive (γδ + ) cells were identified in the gate of blast lymphocytes. Gamma interferon, tumor necrosis factor alpha, interleukin-4 (IL-4), and IL-10 levels in supernatants and serum anti-PT IgG levels were determined using enzyme-linked immunosorbent assay (ELISA). The net percentage of CD3 + blasts in cultures with B. pertussis in the group vaccinated with wP was higher than that in the group vaccinated with the wP low vaccine (medians of 6.2% for the wP vaccine and 3.9% for the wP low vaccine; P = 0.029). The frequencies of proliferating CD4 + , CD8 + , and γδ + cells, cytokine concentrations in supernatants, and the geometric mean titers of anti-PT IgG were similar for the two vaccination groups. There was a significant difference between the T-cell subpopulations for B. pertussis and PHA cultures, with a higher percentage of γδ + cells in the B. pertussis cultures ( P < 0.001). The overall data did suggest that wP vaccination resulted in modestly better specific CD3 + cell proliferation, and γδ + cell expansions were similar with the two vaccines.