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      Intranasal immunization with AFCo1 induce systemic, mucosal and memory immune response in neonatal mice Translated title: Inmunización intranasal con AFCo1 induce respuesta inmune de memoria, sistemica y mucosal en ratones neonatal

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          Abstract

          Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n.) route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay) PL1 (Proteoliposome) from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1) by nasal route in neonatal mice. They were immunized i.n. 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL) was significantly higher than AFPL1 (1107 U/mL). AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i.n. immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i.n. dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory.

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          Neonatal and early life vaccinology.

          Preclinical and human vaccine studies indicate that, although neonatal immunisation does not generally lead to rapid and strong antibody responses, it may result in an efficient immunological priming, which can serve as an excellent basis for future responses. The apparent impairment of CD4 and CD8 T-cell function in early life seems to result from suboptimal antigen-presenting cells-T cell interactions, which can be overcome by use of specific adjuvants or delivery systems. Although persistence of maternal antibodies may limit infant antibody responses, induction of T-cell responses largely remain unaffected by these passively transferred antibodies. Thus, neonatal priming and early boosting with vaccine formulations optimised for sufficient early life immunogenicity and maximal safety profiles, could allow better control of the huge infectious disease burden in early life.
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            Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba.

            The Cuban vaccine, first in the world with proven efficacy against group B-caused disease, is based on outer membrane proteins from B meningococci capable of inducing long-lasting and high-titered bactericidal antibodies in humans. This bactericidal activity has a wide spectrum against all pathogenic group B Neisseria meningitidis tested. A randomized, double-blind controlled trial of the vaccine efficacy was performed during 1987-1989 with 106,000 10-14 years old students from 197 boarding schools in seven provinces. The efficacy obtained was 83% (chi 2, p less than 0.002; Fischer exact, p less than 0.001). In a second field trial including 133,600 persons from 5 months to 24 years of age in Ciego de Avila province (30 cases/10(5) inhabitants, the highest incidence rate in Cuba) by comparing vaccinated and non-vaccinated population after 2.5 years of observation and careful follow-up, the efficacy and safety was confirmed. Because of these results and because of the very low reactogenicity of the vaccine, the Ministry of Public Health took the advice of the Scientific Council to vaccinate all children between 3 months and 6 years of age in the most affected provinces. No severe or long lasting reactions to the vaccine were observed after the millions of doses administered. The efficacy of vaccination varied in the provinces between 83% and 94%, among age groups ranging from 3 months and 20 years. After 3 years of massive application no severe reactions occurred and one of the most severe epidemics has been practically eradicated.
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              Interactions of proteoliposomes from serogroup B Neisseria meningitidis with bone marrow-derived dendritic cells and macrophages: adjuvant effects and antigen delivery.

              Exposure to proteoliposomes from serogroup B Neisseria meningitidis (PL) induced up-regulation of MHC-II, MHC-I, CD40, CD80 and CD86 expression on the surface of murine bone marrow-derived dendritic cells (DC). CD40, CD80 and CD86 were up-regulated on bone marrow-derived macrophages (MPhi) upon stimulation with PL. Both DC and MPhi released TNFalpha, but only DC produced IL12(p70) in response to PL. A small increase in the expression of MHC-II, CD40 and CD86, as well as production of IL12(p70), was observed on the cell surface of DC, but not MPhi from LPS-non-responder C3H/HeJ after exposure to PL. DC, but not MPhi, incubated with PL containing ovalbumin (PL-OVA) presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas. These data clearly indicate that PL exert an immunomodulatory effect on DC and MPhi, with some contribution of non-LPS components besides the main role of LPS. The work also shows the potential of PL as a general system to deliver antigens to DC for presentation to CD4+ and CD8+ T-cells.
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                Author and article information

                Contributors
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                Journal
                vac
                Vaccimonitor
                Vaccimonitor
                Finlay Ediciones (Ciudad de la Habana )
                1025-0298
                August 2009
                : 18
                : 2
                : 81-83
                Affiliations
                [1 ] Finlay Institute Cuba
                Article
                S1025-028X2009000200009
                fb1c29c7-187d-4bb6-a542-d56244fe6130

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Cuba

                Self URI (journal page): http://scielo.sld.cu/scielo.php?script=sci_serial&pid=1025-028X&lng=en
                Categories
                BIOLOGY

                General life sciences
                Neisseria meningitidis,Outer membrane vesicle,Proteoliposome,AFCo1,AFPL1,Neonatal immunization

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