Immune Responses to Irradiated Pneumococcal Whole Cell Vaccine.

Eunbyeol Ko,Min Yong Jwa,Sungho Jeong,Sun Kyung Kim,Seung Hyun Han,Ho Seong Seo,Ki Bum Ahn,Ye-Eun Ha,A Reum Kim,Soyoung Jeong,Cheol-Heui Yun

doi:10.3390/vaccines9040405

Abstract

Streptococcus pneumoniae (pneumococcus) can cause respiratory and systemic diseases. Recently, γ-irradiation-inactivated, non-encapsulated, intranasal S. pneumoniae (r-SP) vaccine has been introduced as a novel serotype-independent and cost-effective vaccine. However, the immunogenic mechanism of r-SP is poorly understood. Here, we comparatively investigated the protective immunity and immunogenicity of r-SP to the heat-(h-SP) or formalin-inactivated vaccine (f-SP) without adjuvants. Mice were intranasally immunized with each vaccine three times and then challenged with a lethal dose of S. pneumoniae TIGR4 strain and then subsequently evaluated for their immune responses. Immunization with r-SP elicited modestly higher protection against S. pneumoniae than h-SP or f-SP. Immunization with r-SP enhanced pneumococcal-specific IgA in the nasal wash and IgG in bronchoalveolar lavage fluid. Immunization with r-SP enhanced S. pneumoniae-specific IgG, IgG1, and IgG2b in the serum. r-SP more potently induced the maturation of dendritic cells in the cervical lymph nodes than h-SP or f-SP. Interestingly, populations of follicular helper T cells and IL-4-producing cells were potently increased in cervical lymph nodes of r-SP-immunized mice. Collectively, r-SP could be an effective intranasal, inactivated whole-cell vaccine in that it elicits S. pneumoniae-specific antibody production and follicular helper T cell activation leading to protective immune responses against S. pneumoniae infection.

Highlights

Streptococcus pneumoniae (S. pneumoniae; pneumococcus) is a facultative anaerobic Gram-positive bacterium that can reside asymptomatically in healthy carriers, normally colonizing in the nasopharynx
capsular polysaccharides (C-PS) is known to interfere with the phagocytic activity of the host immune cells and anti-C-PS antibodies confer protective immunity against pneumococcal infections
We evaluated aWnedecvoamlupaatreeddatnhde pcoromtepcatrievde itmhempurontietyctoivfer-iSmPmaguaniintystoitfsre-SnPcaapgsauinlastteidts encapsulated parent strainstirnafienct(iToInGwR4it)hintfheocsteioonfwhi-tShPthaonsde fo-fSPh.-SMPiacnedwfe-SreP.iMntircaenwasearlelyinimtra-nasally immumunized with nr-iSzPed, hw-SiPth, orr-Sf-PS,Ph-fSoPr,thorefe-StiPmfeosr othnrdeaeytsim0,e7s,oandd1a4y.sT0h,e7r,eawnder1e4n.oTsheerrieouwsere no serious adverse effectsadovf earnsye oeffethcetsvoafcacinnyatoiof nths,esvuacchciansamtioonrsta, lsituychoraws meigohrttaloitsys o(Fr iwguerigeh1tAlo).ss (Figure 1A)

Summary

Introduction

Streptococcus pneumoniae (S. pneumoniae; pneumococcus) is a facultative anaerobic Gram-positive bacterium that can reside asymptomatically in healthy carriers, normally colonizing in the nasopharynx. Pneumococcal pneumonia is a major cause of global hospitalization and mortality. It results in approximately 800,000 deaths per year among children [3,4]. C-PS is known to interfere with the phagocytic activity of the host immune cells and anti-C-PS antibodies confer protective immunity against pneumococcal infections. It has become a major target of the pneumococcal vaccine [8]. Its structural variations account for different immunological serotypes of pneumococcus [9]

Methods

Results

Conclusion