Pulmonary delivery of a targeted mucosal nanocarrier vaccine for pneumonia

• Grant number: 16/50413-8
• Support type: Regular Research Grants
• Duration: March 01, 2018 - February 28, 2021
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Cooperation agreement: MRC, UKRI
• Principal Investigator: Viviane Maimoni Gonçalves
• Grantee: Viviane Maimoni Gonçalves
• Principal investigator abroad: Imran Saleem
• Institution abroad: Liverpool John Moores University (LJMU), England
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae utilizes as a portal of entry into the body causing community acquired-pneumonia (CAP), bacteraemia, meningitis and sepsis (invasive pneumococcal disease, IPD). Current pneumococcal conjugate vaccine (PCV13) comprises 13 of the most common S. pneumoniase serotypes and is administered via the parental route resulting in low levels of lung mucosal immunity. Several trials indicated the efficacy of PCVs against CAP to be lower than IPD. Hence, pneumococcal disease to have a high burden due to limited protection against the total number of serotypes, variation in serotype distribution worldwide and the occurrence of non-vaccine serotype replacement in S. pneumoniase carriage. This led to development of protein antigens such as recombinant pneumococcal surface protein A (PspA), genetically detoxified pneumolysin (PdT) and PspA - PdT fusion protein. These proteins provide serotype independent protection in order to counter replacement disease. Moreover, delivery in a nanocarrier system directly to the lung dendritic cells (DCs) can enhance mucosal and systemic. We will investigate polymer- based nanoparticle (NPs) composed of two polymers in a layer-by-layer approach, as they are biodegradable and biocompatible with tissues/cells, promote the uptake of protein antigens by CDs and as adjuvants aiding in activating cellular and humoral immune responses, potentially reduce the quantity of antigen required and number of vaccine administrations. Lung mucosal immunization offers the advantage of needle-free vaccination, reducing blood-borne infections, and formulated as dry powders (DP) eliminates cold-chain requirements while maintaining antigen stability and integrity. The NPs will be formulated within biocompatible excipients (carbohydrates), amino acids, and combinations) generating DP nanocomposite microparticle carriers (NCMPs) of suitable size (1-5um) for deposition in the respirable tract. The excipients protect the NPs and against the shear forces and increased temperatures during spraying and aides in NPs dispersion in the lung lining fluid for targeting DCs and antigen stability during storage. LJMU will investigate NPs and NCMPs formulations with protein antigens provided by Institute Butantan. The optimum formulation will evaluated for cellular and humoral immune responses in mice, and protection against intranasal challenge of S. pneumoniase, compared to antigen alone at Institute Butantan. (AU)