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Evaluation of the efficacy of PspA (pneumococcal surface protein A) in a co-colonization model with different strains of Streptococcus pneumoniae

Grant number: 13/17699-7
Support type:Regular Research Grants
Duration: December 01, 2013 - May 31, 2016
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Eliane Namie Miyaji
Grantee:Eliane Namie Miyaji
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae is an important human pathogen, causing severe diseases such as meningitis, pneumonia, bacteremia and sepsis. The currently available vaccines are based on the response to the capsular polysaccharide and they have some shortcomings, such as high production cost and coverage restricted to the serotypes included in the formulation. The use of the 7-valent conjugate vaccine led to an impressive reduction of infections caused by vaccine serotypes, but there was also a rapid substitution of disease caused by non-vaccine serotypes. The development of new vaccines against pneumococci is thus still a priority and alternative strategies are being evaluated, such as the use of protein antigens. Several recombinant proteins expressed in Escherichia coli are being studied as vaccine antigens and PspA (Pneumococcal surface protein A) is one of the most promising candidates. PspA shows variability in different strains and our group has shown that some PspA variants induce antibodies with broader cross-reactivity with different pneumococcal strains. We have also demonstrated that these PspA variants are able to induce protection in mice against an intranasal lethal challenge model and against colonization of the nasopharynx. We now propose to test efficacy in a mouse model of co-colonization of the nasopharynx using isolates with the same genetic background, but expressing different PspAs. Initially, strains expressing PspA from clade 1 (PspA1) and clade 4 (PspA4) will be constructed through the transformation of the laboratory strain TIGR4 (PspA clade 3 - PspA3), using the "Janus Cassette" for the allelic exchange. Mice will be immunized with recombinant PspAs that induce antibodies with reduced cross-reactivity (PspA1, PspA2 and PspA3) or with broad cross-reactivity (PspA4 and PspA5) and then challenged with a mixture of two strains expressing different PspAs. The two strains will be identified by the resistance to distinct antibiotics. The hypothesis is that animals immunized with a variant that induces antibodies with low cross-reactivity would be able to control only the colonization by bacteria expressing the exact same variant and would be colonized by pneumococci expressing the heterologous PspA. On the other hand, animals immunized with the variant that induces antibodies with broad cross-reactivity would have reduced colonization by both challenge strains. The use of a vaccine that could control colonization by bacteria expressing different PspAs would reduce the possibility of the phenomenon of substitution of prevalent strains that has already occurred with the use of the polysaccharide conjugate vaccine. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TOSTES, RAFAELLA O.; RODRIGUES, TASSON C.; DA SILVA, JOSEFA B.; SCHANOSKI, ALESSANDRA S.; OLIVEIRA, MARIA LEONOR S.; MIYAJI, ELIANE N. Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae. PLoS One, v. 12, n. 1 JAN 19 2017. Web of Science Citations: 2.

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