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Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice.

ABSTRACT: PURPOSE:A pep27 mutant may be able to elicit mucosal immunity against pneumococcal diseases, and could be employed as an inexpensive attenuated vaccine. However, this particular mutant contains an erythromycin-resistance marker. The purpose of the current study is to develop a markerless pep27 mutant and assess whether this inactivated mutant is able to induce mucosal immunity. MATERIALS AND METHODS:Mice were vaccinated intranasally with the inactivated markerless pep27 mutant every 2 weeks for a total of three times, after which time serum samples were analyzed for antibody titers. The mice were then challenged with a lethal D39 strain and their survival time was measured. The cross-reactivity of the antisera against pep27 was also compared to other mutant serotypes. RESULTS:Intranasal immunization of mice with the inactivated markerless pep27 mutant provides effective protection and rapidly cleared bacterial colonization in vivo. Moreover, antisera raised against the pep27 mutant may cross-react with several other serotype strains. CONCLUSION:Intranasal immunization with the inactivated pep27 mutant may be able to provide mucosal immunity, and could represent an efficient mucosal vaccine.

SUBMITTER: Choi SY

PROVIDER: S-EPMC3623503 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice.

Choi Sang-Yoon SY Tran Thao Dang-Hien TD Briles David E DE Rhee Dong-Kwon DK

Clinical and experimental vaccine research 20130115 1

<h4>Purpose</h4>A pep27 mutant may be able to elicit mucosal immunity against pneumococcal diseases, and could be employed as an inexpensive attenuated vaccine. However, this particular mutant contains an erythromycin-resistance marker. The purpose of the current study is to develop a markerless pep27 mutant and assess whether this inactivated mutant is able to induce mucosal immunity.<h4>Materials and methods</h4>Mice were vaccinated intranasally with the inactivated markerless pep27 mutant eve ...[more]

PMID: 23596592

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Project description:Pneumococcal disease remains a global burden, with current conjugated vaccines offering protection against the common serotype strains. However, there are over 100 serotype strains, and serotype replacement is now being observed, which reduces the effectiveness of the current vaccines. Pneumococcal surface protein A (PspA) has been investigated as a candidate for new serotype-independent pneumococcal vaccines, but requires adjuvants and/or delivery systems to improve protection. Polymeric nanoparticles (NPs) are biocompatible and, besides the antigen, can incorporate mucoadhesive and adjuvant substances such as chitosans, which improve antigen presentation at mucosal surfaces. This work aimed to define the optimal NP formulation to deliver PspA into the lungs and protect mice against lethal challenge. We prepared poly(glycerol-adipate-co-ω-pentadecalactone) (PGA-co-PDL) and poly(lactic-co-glycolic acid) (PLGA) NPs using an emulsion/solvent evaporation method, incorporating chitosan hydrochloride (HCl-CS) or carboxymethyl chitosan (CM-CS) as hybrid NPs with encapsulated or adsorbed PspA. We investigated the physicochemical properties of NPs, together with the PspA integrity and biological activity. Furthermore, their ability to activate dendritic cells in vitro was evaluated, followed by mucosal immunization targeting mouse lungs. PGA-co-PDL/HCl-CS (291 nm) or CM-CS (281 nm) NPs produced smaller sizes compared to PLGA/HCl-CS (310 nm) or CM-CS (299 nm) NPs. Moreover, NPs formulated with HCl-CS possessed a positive charge (PGA-co-PDL +17 mV, PLGA + 13 mV) compared to those formulated with CM-CS (PGA-co-PDL -20 mV, PLGA -40 mV). PspA released from NPs formulated with HCl-CS preserved the integrity and biological activity, but CM-CS affected PspA binding to lactoferrin and antibody recognition. PspA adsorbed in PGA-co-PDL/HCl-CS NPs stimulated CD80+ and CD86+ cells, but this was lower compared to when PspA was encapsulated in PLGA/HCl-CS NPs, which also stimulated CD40+ and MHC II (I-A/I-E)+ cells. Despite no differences in IgG being observed between immunized animals, PGA-co-PDL/HCl-CS/adsorbed-PspA protected 83% of mice after lethal pneumococcal challenge, while 100% of mice immunized with PLGA/HCl-CS/encapsulated-PspA were protected. Therefore, this formulation is a promising vaccine strategy, which has beneficial properties for mucosal immunization and could potentially provide serotype-independent protection.

Dataset Information

Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice.

Publications

Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice.

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