Immune responses and protection against Streptococcus pneumoniae elicited by recombinant Bordetella pertussis adenylate cyclase (CyaA) carrying fragments of pneumococcal surface protein A, PspA

Author(s)

Carneiro, Giovanna Brito ; Castro, Julia Tavares ; Davi, Marilyne ; Miyaji, Eliane Namie ; Ladant, Daniel ; Oliveira, Maria Leonor Sarno

• Document type: Journal article
• Source: Vaccine; v. 41, n. 28, p. 13-pg., 2023-06-17.

Abstract

Streptococcus pneumoniae is a common agent of important human diseases such as otitis media, pneumo-nia, meningitis and sepsis. Current available vaccines that target capsular polysaccharides induce protec-tion against invasive disease and nasopharyngeal colonization in children, yet their efficacy is limited to the serotypes included in the formulations. The virulence factor Pneumococcal Surface Protein A (PspA) interacts with host immune system and helps the bacteria to evade phagocytosis. Due to its essential role in virulence, PspA is an important vaccine candidate. Here we have tested a delivery system based on the adenylate cyclase toxin of Bordetella pertussis (CyaA) to induce immune responses against PspA in mice. CyaA was engineered to express fragments of the N-terminal region of PspAs from clades 2 and 4 (A2 and A4) and the resulting proteins were used in immunization experiments in mice. The recombinant CyaA-A2 and CyaA-A4 proteins were able to induce high levels of anti-PspA antibodies that reacted with pneu-mococcal strains expressing either PspA2 or PspA4. Moreover, reactivity of the antibodies against pneu-mococcal strains that express PspAs from clades 3 and 5 (PspA3 and PspA5) was also observed. A formulation containing CyaA-A2 and CyaA-A4 was able to protect mice against invasive pneumococcal challenges with isolates that express PspA2, PspA4 or PspA5. Moreover, a CyaA-A2-A4 fusion protein induced antibodies at similar levels and with similar reactivity as the formulation containing both pro-teins, and protected mice against the invasive challenge. Our results indicate that CyaA-PspA proteins are good candidates to induce broad protection against pneumococcal isolates. & COPY; 2023 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 19/25853-2 - Adenylate cyclase toxin from Bordetella pertussis as an antigen presentation system for the PspA antigen from Streptococcus pneumoniae: characterization of immune responses and protection in mice
• Grantee: Giovanna de Brito Carneiro
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/13134-3 - Recombinant Vaccines against Streptococcus pneumoniae and Bordetella pertussis
• Grantee: Maria Leonor Sarno de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/05671-7 - Development of vaccines against Streptococcus pneumoniae using bacterial components as adjuvants for the PspA antigen
• Grantee: Giovanna de Brito Carneiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/50296-1 - Development of recombinant vaccines against Streptococcus pneumoniae based on the adjuvant activity of the adenylate cyclase toxin from Bordetella pertussis - StrepCyaVac
• Grantee: Maria Leonor Sarno de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/17258-9 - Bordetella pertussis and its components as delivery systems and adjuvants for vaccine development against Streptococcus pneumoniae
• Grantee: Júlia Tavares de Castro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/01701-3 - Evaluation of the adenylate cyclase toxin from Bordetella pertussis as a delivery vector for Streptococcus pneumoniae PspA antigen
• Grantee: Júlia Tavares de Castro
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)