Addition of adjuvant to DTaP modulates vaccine-induced immunological responses but is insufficient to improve protection in CD-1 mice

Weaver, K. L.; Pyles, G. M.; Dublin, S. R.; Huckaby, A. B.; Miller, S. J.; Gutierrez, M. d. l. P.; Sen-Kilic, E.; Witt, W. T.; Boehm, D. T.; Damron, F. H.; Barbier, M.

doi:10.1101/2023.03.03.530983

bioRxiv · 10.1101/2023.03.03.530983

Addition of adjuvant to DTaP modulates vaccine-induced immunological responses but is insufficient to improve protection in CD-1 mice

Weaver, K. L.·Pyles, G. M.·Dublin, S. R.·Huckaby, A. B.·Miller, S. J.·Gutierrez, M. d. l. P.·Sen-Kilic, E.·Witt, W. T.·Boehm, D. T.·Damron, F. H.·Barbier, M.

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Abstract

3.1Pertussis is a vaccine-preventable respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. While vaccination rates remain high in developed countries, incidence of pertussis has increased following the transition from wP vaccines to aP vaccines. The reemergence of pertussis is attributed, in part, to waning immunity induced by aP vaccination. Therefore, the objective of this work was to determine if addition of adjuvant to DTaP can modulate the immune response and improve protection compared to DTaP alone. In this study we immunized outbred, female CD-1 mice with 1/320th the human dose of vehicle control, DTaP, and DTaP supplemented with adjuvant. Markers of early vaccine-induced memory were measured using a chemokine assay or by flow cytometry. Protection was assessed by measuring serological responses and quantifying bacterial burden in the respiratory tract at day 3 post-challenge. From this work we identified a partially protective aP vaccine dose to use for vaccination and challenge studies. We observed that MPLA and SWE promote robust anti-B. pertussis antibody responses and stimulate significant increases in early markers of vaccine-induced memory such as CXCL13, FDCs, and TFH cells. Quil-A induced Th1 responses compared to DTaP alone, but none of the adjuvants improved protection against challenge with B. pertussis. Overall, the data suggests that addition of adjuvant modulates the protective immune responses induced by aPs. Further studies are needed to evaluate the B cell compartment and longevity of protection.

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Weaver, K. L., Pyles, G. M., Dublin, S. R., Huckaby, A. B., Miller, S. J., Gutierrez, M. d. l. P., Sen-Kilic, E., Witt, W. T., Boehm, D. T., Damron, F. H., Barbier, M.. 2023-03-04. Addition of adjuvant to DTaP modulates vaccine-induced immunological responses but is insufficient to improve protection in CD-1 mice. https://doi.org/10.1101/2023.03.03.530983

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