Biology subjects

Gaillard, M. E.

Publications and source records attributed to Gaillard, M. E..

2 recordsLinked to original sources

bioRxiv2024

Use of Mucosally Administered Outer Membrane Vesicles Derived from Bordetella pertussis to Diminish Nasal Bacterial Colonization

BackgroundWe previously identified Bordetella pertussis-derived outer membrane vesicles (OMVs) as a promising immunogen for improving pertussis vaccines. In this study, we evaluated the efficacy of our vaccine prototype in immunization strategies aimed at reducing disease transmission by targeting colonization in the upper airways while maintaining protection against severe disease by reducing colonization in the lower respiratory tract. MethodsWe assessed different mucosal administration strategies in a murine model, including homologous 2-dose schedules and heterologous prime-boost strategies combining intramuscular (IM) systemic immunization with mucosal routes (intranasal (IN) or sublingual (SL)). We utilized mucosal c-di-AMP and/or systemic alum adjuvants to formulate the OMV vaccine prototype. A homologous IM immunization schedule and commercial vaccines were used for comparison. ResultsAll tested heterologous schemes induced higher levels of specific IgG with significant avidity, as well as high levels of IgG1 and IgG2 compared, to corresponding homologous 2-dose schemes via mucosal routes (OMVIN-IN or OMVSL-SL). High IgA levels were observed post-B. pertussis challenge following OMVIN-IN treatments and heterologous treatments where the second dose was administered via a mucosal route. Furthermore, schemes involving the intranasal route, whether in a homologous or heterologous scheme, induced the highest levels of IL-17 and IFN-{gamma}. Accordingly, these schemes showed superior efficacy against nasal colonization than the commercial vaccines. Specifically, homologous intranasal immunization exhibited the highest protective capacity against nasal colonization while maintaining an excellent level of protection in the lower respiratory tract. To enhance the protective capacity against nasal colonization further, we conducted a comparative analysis of formulations containing different adjuvants (c-di-AMP, alum, or a combination of both) administered via homologous intranasal routes. These assays revealed that the use of alum, either alone or in combination with c-di-AMP, did not enhance the immune protective capacity. ConclusionsAll the experiments presented here highlight that the use of OMVs, regardless of the scheme utilized, with the exception of OMVSL-SL, outperformed acellular pertussis (aP) vaccines, achieving a greater reduction in bacterial colonization in the upper respiratory tract (p<0.001).

immunology↗

bioRxiv2023

Heterologous booster with a novel formulation containing glycosylated trimeric S protein is effective againstOmicron

In this study, we evaluated the efficacy of a heterologous three-dose vaccination schedule against the Omicron BA.1 SARS-CoV-2 variant infection using a mouse intranasal challenge model. The vaccination schedules tested in this study consisted of a primary series of 2 doses covered by two commercial vaccines: an mRNA-based vaccine (mRNA1273) or a non-replicative vector-based vaccine (AZD1222/ChAdOx1, hereafter referred to as AZD1222). These were followed by a heterologous booster dose using one of the two vaccine candidates previously designed by us: one containing the glycosylated and trimeric spike protein (S) from the ancestral virus (SW-Vac 2g), and the other from the Delta variant of SARS-CoV-2 (SD-Vac 2g), both formulated with Alhydrogel as an adjuvant. For comparison purposes, homologous three-dose schedules of the commercial vaccines were used. The mRNA-based vaccine, whether used in heterologous or homologous schedules, demonstrated the best performance, significantly increasing both humoral and cellular immune responses. In contrast, for the schedules that included the AZD1222 vaccine as the primary series, the heterologous schemes showed superior immunological outcomes compared to the homologous 3-dose AZD1222 regimen. For these schemes no differences were observed in the immune response obtained when SW-Vac 2g or SD-Vac 2g were used as a booster dose. Neutralizing antibody levels against Omicron BA.1 were low, especially for the schedules using AZD1222. However, a robust Th1 profile, known to be crucial for protection, was observed, particularly for the heterologous schemes that included AZD1222. All the tested schedules were capable of inducing populations of CD4 T effector, memory, and follicular helper T lymphocytes. It is important to highlight that all the evaluated schedules demonstrated a satisfactory safety profile and induced multiple immunological markers of protection. Although the levels of these markers were different among the tested schedules, they appear to complement each other in conferring protection against intranasal challenge with Omicron BA.1 in K18-hACE2 mice. In summary, the results highlight the potential of using the S protein (either ancestral Wuhan or Delta variant)-based vaccine formulation as heterologous boosters in the management of COVID-19, particularly for certain commercial vaccines currently in use.

immunology↗