The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines

Ramiro Ortiz Moyano; Fernanda Raya Tonetti; Kohtaro Fukuyama; Mariano Elean; Mikado Tomokiyo; Yoshihito Suda; Vyacheslav Melnikov; Haruki Kitazawa; Julio Villena

doi:10.3390/vaccines11030611

The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines

Vaccines (Basel). 2023 Mar 8;11(3):611. doi: 10.3390/vaccines11030611.

Authors

Ramiro Ortiz Moyano¹, Fernanda Raya Tonetti¹, Kohtaro Fukuyama^{2

3}, Mariano Elean¹, Mikado Tomokiyo^{2

3}, Yoshihito Suda⁴, Vyacheslav Melnikov⁵, Haruki Kitazawa^{2

3}, Julio Villena^{1

2}

Affiliations

¹ Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucumán 4000, Argentina.
² Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
³ Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
⁴ Department of Food, Agriculture and Environment, Miyagi University, Sendai 980-8572, Japan.
⁵ Gabrichevsky Research Institute for Epidemiology and Microbiology, 125212 Moscow, Russia.

Abstract

Previously, we demonstrated that nasally administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or its bacterium-like particles (BLPs) increase the resistance of mice against bacterial and viral respiratory pathogens by modulating the innate immunity. In this work, we evaluated the ability of Cp and BLPs to stimulate alveolar macrophages, and to enhance the humoral immune response induced by a commercial vaccine against Streptococcus pneumoniae. In the first set of experiments, Cp or the BLPs were incubated with primary cultures of murine alveolar macrophages and the phagocytic activity, and the production of cytokines was evaluated. The results revealed that Cp and BLPs were efficiently phagocyted by respiratory macrophages and that both treatments triggered the production of TNF-α, IFN-γ, IL-6, and IL-1β. In the second set of experiments, 3-week-old Swiss mice were intranasally immunized at days 0, 14, and 28 with the pneumococcal vaccine Prevenar^®13 (PCV), Cp + PCV, or BLPs + PCV. On day 33, samples of bronco-alveolar lavages (BAL) and serum were collected for the study of specific antibodies. In addition, immunized mice were challenged with S. pneumoniae serotypes 6B or 19F on day 33 and sacrificed on day 35 (day 2 post-infection) to evaluate the resistance to the infection. Both Cp + PCV and BLPs + PCV groups had higher specific serum IgG and BAL IgA antibodies than the PCV control mice. In addition, the mice that were immunized with Cp + PCV or BLPs + PCV had lower lung and blood pneumococcal cell counts as well as lower levels of BAL albumin and LDH, indicating a reduced lung damage compared to the control mice. Improved levels of anti-pneumococcal antibodies were also detected in the serum and BAL samples after the challenges with the pathogens. The results demonstrated that C. pseudodiphtheriticum 090104 and its bacterium-like particles are capable of stimulating the respiratory innate immune system serving as adjuvants to potentiate the adaptive humoral immune response. Our study is a step forward in the positioning of this respiratory commensal bacterium as a promising mucosal adjuvant for vaccine formulations aimed at combating respiratory infectious diseases.

Keywords: Corynebacterium pseudodiphtheriticum; alveolar macrophages; bacterium-like particles; mucosal adjuvant; respiratory infection.

Abstract

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