Whole Cell Pneumococcal Vaccine Using Porcine Lung Surfactant As Adjuvant Protects Mice Against Pneumococcal Nasopharingeal Colonization
Silva, APGB1; Sbrogio-Almeida, ME1; Liberman, C1; Takagi, M1; Maimoni Gonçalves, V1; Dmitri Iourtov1; Kubrusly, FS1; Richard Malley2; Porter Anderson3 ; Leite, LCC1; Dias, WO1
1Instituto Butantan – Centro de Biotecnologia; 2Childrens Hospital Boston and Harvard Medical School; 3University of Rochester, NY
The infections caused by Streptococcus pneumoniae are responsible for ten million deaths every year around the world. The currently available pneumococcal vaccines either offer low protection for the high-risk groups or are too expensive for general vaccination in developing countries. It has been proposed that intranasal immunization with a killed whole cell vaccine derived from a nonencapsulated mutant of Streptococcus pneumoniae (originally a serotype 2 strain, autolisine negative, and carrying a pneumolisin defective gene) can be used in combination with CT or CTB as adjuvant for protection against pneumococcal colonization. We studied the adjuvant effect of an exogenous natural surfactant from minced porcine lungs, in the humoral immune response and protection of mice, elicited by this whole cell pneumococcal vaccine. Although lung surfactant primary function is to reduce surface tension in the alveoli, some studies indicate that pulmonary surfactant can also influence the immune function. The cellular pneumococcal vaccine administred intranasally mixed with pig lung surfactant elicited significantly higher serum IgG antibodies, evaluated by ELISA against vaccine antigens, when compared with the vaccine alone (IgG antibodies titers 293 and 136, respectively; Mann Whitney p= 0.04). When injected intraperitoneally, the vaccine with surfactant induced significantly higher serum IgG antibodies when, compared with the surfactant alone (IgG antibodies titers 720 and 186, respectively; Mann Whitney p= 0.0007). This preparation administered intranasally showed a protective effect in mice, against an intranasal challenge with a capsulated pneumococci (strain 603/serotype 6B), significantly reducing the nasopharyngeal colonization, in relation to the surfactant alone (group immunized with Vaccine+surfactant = 2125 CFU/ml and with surfactant = 10150 CFU/ml; Mann Whitney p = 0.0033). Taken together, our results are promising, and show a new perspective for adjuvants and pneumococcal vaccines.
Supported by FAPESP
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