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The whole-cell pertussis vaccine imposes a broad effector B cell response in mouse heterologous prime-boost settings
Viviana Valeri, … , Jean-Claude Weill, Claude-Agnès Reynaud
Viviana Valeri, … , Jean-Claude Weill, Claude-Agnès Reynaud
Published September 22, 2022
Citation Information: JCI Insight. 2022;7(21):e157034. https://doi.org/10.1172/jci.insight.157034.
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Research Article Immunology Vaccines

The whole-cell pertussis vaccine imposes a broad effector B cell response in mouse heterologous prime-boost settings

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Abstract

ÍSince the introduction of new generation pertussis vaccines, resurgence of pertussis has been observed in many developed countries. Former whole-cell pertussis (wP) vaccines are able to protect against disease and transmission but have been replaced in several industrialized countries because of their reactogenicity and adverse effects. Current acellular pertussis (aP) vaccines, made of purified proteins of Bordetella pertussis, are efficient at preventing disease but fail to induce long-term protection from infection. While the systemic and mucosal T cell immunity induced by the 2 types of vaccines has been well described, much less is known concerning B cell responses. Taking advantage of an inducible activation-induced cytidine deaminase fate-mapping mouse model, we compared effector and memory B cells induced by the 2 classes of vaccines and showed that a stronger and broader memory B cell and plasma cell response was achieved by a wP prime. We also observed that homologous or heterologous vaccine combinations that include at least 1 wP administration, even as a booster dose, were sufficient to induce this broad effector response, thus highlighting its dominant imprint on the B cell profile. Finally, we describe the settlement of memory B cell populations in the lung following subcutaneous wP prime vaccination.

Authors

Viviana Valeri, Akhésa Sochon, Clara Cousu, Pascal Chappert, Damiana Lecoeuche, Pascal Blanc, Jean-Claude Weill, Claude-Agnès Reynaud

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Figure 6

Three different signatures of memory B cells were identified by single-cell RNA-Seq analysis in vaccinated mice.

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Three different signatures of memory B cells were identified by single-c...
(A) The expression of CD73, CD80, and PD-L2 was determined on dLN EYFP+GL7– memory B cells by flow cytometry 50 days after boost from AID-Cre-EYFP mice that were primed and boosted (day 30) with homologous and heterologous combinations of the aP and wP vaccines or injected with alum (ctr). Three doses of tamoxifen were administrated at days 7, 10, and 31. Representative flow cytometry plots are shown for aP:aP and wP:wP conditions. CD73+CD80+ and PD-L2+CD80+ memory EYFP+ populations in dLNs are shown in the graphs for all vaccine combinations. (B) Uniform manifold approximation and projection (UMAP) and clustering of 707 EYFP+ GC and 1,962 EYFP+ memory sorted B cells analyzed by scRNA-Seq from dLNs of AID-Cre-EYFP mice 50 days after boost injection, and tamoxifen administration on days 7, 10, and 31, from 2 aP:aP-, 3 aP:wP-, 3 wP:aP-, and 2 wP:wP-immunized mice. (C) Selected gene expression for the 6 different clusters (numbered 0–5) is presented in dot plot scale on normalized unique molecular identifier (UMI) counts. Frequencies (D) and absolute numbers (E) of EYFP+ memory B cells within clusters 0, 3, and 4 are shown for the 4 vaccine combinations. (F) Isotype profile determined by flow cytometry during cell sorting is shown for the EYFP+ memory B cells from clusters 0, 3, and 4. Means (±SEM) are shown in panels A, D, and E.

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