Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring

ABSTRACT

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 μg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.

KEYWORDS:

• SARS-CoV-2
• receptor-binding domain (RBD)
• outer membrane vesicles (OMVs)
• Neisseria meningitidis
• adjuvants
• cross-reaction

Acknowledgments

The authors thank the isolation of N. meningitidis C:2a:P1.5 strain by Dr Ana Paula Lemos (Bacteriology Center, Adolfo Lutz Institute, São Paulo, SP, Brazil), and the plasmids donations for RBD production, from Dr Florian Krammer (Icahn School of Medicine of Mount Sinai Hospital, New York, NY, USA) (RBD-Wuhan) and from Dr Silvia Beatriz Boscardin (Parasitology Department of Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil) (RBD-Omicron) to Dr Carlos Roberto Prudencio.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2346963.

Additional information

Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP [grant numbers 2018/04202-0, 2021/11936-3, 2022/05566-1], Conselho Nacional de Desenvolvimento Científico e Tecnológico/CNPq [grant number 305301/2022-5], Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/CAPES (finance code 001) and São Paulo Secretary of Health/FESIMA.