Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

• Published in: Vaccine Vol. 35; no. 39; pp. 5256 - 5263
• Main Authors: Misiak, Alicja, Leuzzi, Rosanna, Allen, Aideen C., Galletti, Bruno, Baudner, Barbara C., D'Oro, Ugo, O'Hagan, Derek T., Pizza, Mariagrazia, Seubert, Anja, Mills, Kingston H.G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 18.09.2017; Elsevier Limited
• Subjects: Adjuvant; Adjuvants, Immunologic; Adsorption; Alum; Aluminum; Aluminum hydroxide; Animal models; Animals; Antibodies; Antigens; Bordetella pertussis - immunology; Bordetella pertussis - pathogenicity; CHO Cells; Cough; Cricetulus; Developed countries; Diagnostic software; Diagnostic systems; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Helper cells; Immune response (humoral); Immune system; Immunity; Immunity, Humoral - immunology; Immunity, Humoral - physiology; Immunoassay; Immunoglobulin G; Infections; Ligands; Lungs; Lymphocytes T; Membrane Glycoproteins - agonists; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Motivation; Pertussis; Pertussis Vaccine - therapeutic use; Protective immunity; Proteins; Rodents; Th1 Cells - immunology; Th1 Cells - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism; TLR7; TLR7 protein; Toll-Like Receptor 7 - agonists; Toll-Like Receptor 7 - metabolism; Toll-like receptors; Vaccination - methods; Vaccine; Vaccines; Whooping cough; Working groups; Pertussis; Vaccine; Adjuvant; TLR7; Protective immunity
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.08.009

•Adresses protection of adjuvanted acellular pertussis vaccines in the mouse model.•Alum-TLR7a adjuvant induces Th1/Th17 profile and higher IgG2a/b response.•Alum-TLR7a adjuvant enhances protection from bacterial challenge.•Alum-TLR7a adjuvanted vaccines could counteract the recent pertussis resurgence. A resurgence of whooping cough (pertussis) has been observed in recent years in a number of developed countries, despite widespread vaccine coverage. Although the exact reasons of the recurrence of pertussis are not clear, there are a number of potential causes, like antigenic variation in the circulating strains of Bordetella pertussis, changes in surveillance and diagnostic tools, and potential differences in protection afforded by current acellular pertussis (aP) vaccines compared to more reactogenic whole cell (wP) vaccines, which they replaced. Studies in animal models have shown that induction of cellular as well as humoral immune responses are key to conferring effective and long lasting protection against B. pertussis. wP vaccines induce robust Th1/Th17 responses, which are associated with good protection against lung infection. In contrast, aP vaccines induce mixed Th2/Th17 responses. One research option is to modify current aP vaccines with the intention of inducing protective T cell responses, without compromising on their low reactogenicity profile. Here we found that formulation of an aP vaccine with a novel adjuvant based on a Toll-like receptor 7 agonist (TLR7a) adsorbed to aluminum hydroxide (alum) enhanced B. pertussis-specific Th1 and Th17 responses and serum IgG2a/b antibodies, which had greater functional capacity than those induced by aP formulated with alum alone. Furthermore, addition of a TLR7a enhanced the protective efficacy of the aP vaccine against B. pertussis aerosol challenge; protection was comparable to that of a wP vaccine. These findings suggest that alum-TLR7a is a promising adjuvant for clinical development of next generation pertussis vaccines.