Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

Author(s)

Rodrigues, Tasson C. ^[1] ; Oliveira, Maria Leonor S. ^[1] ; Soares-Schanoski, Alessandra ^[1] ; Chavez-Rico, Stefanni L. ^[1] ; Figueiredo, Douglas B. ^[2] ; Goncalves, Viviane M. ^[2] ; Ferreira, Daniela M. ^[3] ; Kunda, Nitesh K. ^{[4, 5]} ; Saleem, Imran Y. ^[5] ; Miyaji, Eliane N. ^[1]

Affiliation

^[1] Inst Butantan, Lab Bacteriol, Sao Paulo, SP - Brazil

^[2] Inst Butantan, Lab Especial Desenvolvimento Vacinas, Sao Paulo, SP - Brazil

^[3] Univ Liverpool Liverpool Sch Trop Med, Resp Infect Grp, Liverpool, Merseyside - England

^[4] Univ New Mexico, Coll Pharm, Dept Pharmaceut Sci, Albuquerque, NM 87131 - USA

^[5] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Formulat & Drug Delivery Res, Liverpool, Merseyside - England

• Document type: Journal article
• Source: PLoS One; v. 13, n. 1 JAN 23 2018.
• Web of Science Citations: 11

Abstract

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-omega-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2. (AU)

• FAPESP's process: 15/06255-6 - Development and production of new pneumococcal vaccines based on recombinant proteins
• Grantee: Viviane Maimoni Gonçalves
• Support type: Regular Research Grants
• FAPESP's process: 14/25436-9 - Nanoparticles containing the antigen PspA (Pneumococcal surface protein A) as a vaccine against pneumococcal pneumonia
• Grantee: Tasson da Costa Rodrigues
• Support type: Scholarships in Brazil - Scientific Initiation