Quantitative Priming with Inactivated Pertussis Toxoid Vaccine in the Aerosol Challenge Model

ABSTRACT Serum antibodies to pertussis toxin (PT) have been shown to be protective against severe pertussis disease, although a specific level of anti-PT antibody that correlates with protection has not been demonstrated. Current animal models such as the intracerebral challenge model have significant limitations in correlating protection to a specific level of anti-PT antibody. This study examines the protective effects of priming with tetranitromethane-inactivated pertussis toxoid (PTx) vaccine in the aerosol challenge model and whether a measurable response to a priming dose of PTx is enough to initiate a protective secondary response when challenged with infection. The correlation of priming with markers of illness such as leukocytosis, weight loss, bacterial proliferation, and mortality after established infection with Bordetella pertussis was explored. BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. Data were analyzed according to the primary immunologic response, differentiating responders (anti-PT immunoglobulin G [IgG] ≥1 μg/ml) from nonresponders (anti-PT IgG <1 μg/ml). Mice that showed evidence of priming on the day of aerosol challenge were able to mount a secondary response to the challenge with a ≥2-fold rise in anti-PT IgG antibody by day 7 and a ≥10-fold rise by day 14 post-aerosol challenge. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge.

QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS

The influence of the immunologic status of the cell donors on the proliferative behavior of rat lymphocytes in the mixed lymphocyte interaction has been studied. Mixed cultures of cells from various parental and F1 combinations having morphologically distinguishable sex chromosomes exhibited unidirectional proliferative reactivity. The mitotic figures were predominately of parental origin. Lymphocytes from donors made tolerant at birth to homologous transplantation isoantigens were specifically unreactive against cells bearing antigens of the tolerance inducing strain, but not to indifferent third party homologous lymphocytes. Cells from animals that had been surgically thymectomized at birth exhibited a markedly and sometimes totally diminished reactivity against homologous lymphocytes. Presensitization of the cell donors resulted in a curtailment of proliferative reactivity in cultures with cells bearing the immunizing antigens. This may reflect the destructive properties that lymphocytes from sensitized animals are known to possess. The results of these experiments show that the proliferative activity of lymphocytes in the mixed lymphocyte interaction accurately reflects the immunologic status of the cell donors, and these findings provide further support for the premise that the mixed lymphocyte interaction represents a primary immunologic response by cells in culture against homologous cells bearing histocompatibility antigens.