Development of a bivalent vaccine against Acinetobacter baumannii (A. baumannii) and Streptococcus agalactiae (S. agalactiae)

Summary

Antimicrobial costs have been increasing steadily every year and special attention has been given by Brazilian public agencies, such as the National Agency of Sanitary Surveillance (ANVISA), to resistant bacterial infections. The study proposal is the development of a bivalent conjugate vaccine against A. baumannii and S. agalactiae which cause a high incidence of infections in hospitals in Brazil. The Streptococcus species also causes meningitis in newborn babies. This vaccine project targets two groups: adults susceptible to hospital-acquired infections, and pregnant women, who are at risk of S. agalactiae infection.  Taking advantage of the skills acquired by Bio-Manguinhos, from Oswaldo Cruz Foundation, in the development of conjugate vaccines for meningococcus, the study intends to develop a vaccine obtained by the chemical conjugation between the capsular polysaccharide of S. agalactiae and the major outer membrane (OM) protein, OmpA, from outer membrane vesicles (OMVs) from A. baumannii. The effectiveness of the vaccine, in inducing protection against the two target bacteria, will be assessed in mice. The proposal goal will be the search of correlates of immunity, through the evaluation of the induced antibody functionality and the changes to adhesion pattern of the two microorganisms to epithelial cell monolayers. Bio-Manguinhos will produce the experimental vaccines, immunize the mice and evaluate the functionality of the induced antibodies to protect against the two vaccine target pathogens. The adhesion test will be also performed by Bio-Manguinhos. NIBSC, the National Control Laboratory of the U.K. will evaluate the quality of glycoconjugate and OMV vaccines and components.

Project outcomes

The main findings of this project to develop a bivalent vaccine to protect against two organisms of significance in Brazil and globally are: 

• The Streptococcus agalactiae polysaccharide production process was optimised and polysaccharide capsule has been obtained of the expected quality described in the literature for Group B Streptococcal serotype Ia.  This component can potentially protect pregnant women and their unborn babies against neonatal meningitis. 

• Outer membrane vesicles (OMVs) were obtained from Acinetobacter baumannii, which can potentially protect critically ill hospital patients from acquiring infections in intensive care settings. 

• Characterisation and proteomic study of A. baumannii's OMV was a great advance, especially in evaluating the effect of detergent-treatment on vesicle size, lipid and protein composition and endotoxin content. This aided the production of safe conjugate vaccine material for the immunisation of mice, and also confirmed the presence of Outer Membrane Protein A (OmpA), the candidate carrier protein, in OMVs made with and without detergent. 

• An adhesion inhibition test to evaluate if vaccine sera can prevent S. agalactiae and A. baumanni from binding to epithelial cells was established as an additional test to evaluate the immune response induced by experimental vaccines. 

The project demonstrated that an experimental conjugate vaccine against two organisms (for which vaccines are not currently available) has the potential to protect against infection. Its further success will depend on improving conjugation reactions and characterisation of the obtained molecules, so a choice can be made to select the best carrier protein to be used. The work developed in a period of so many restrictions also showed the group's ability to seek work solutions that were not previously foreseen and reinforced the value of partnerships with groups with diverse experience and expertise inside and outside Fiocruz.