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Neonatal vaccination with Mycobacterium bovis BCG: potential effects as a priming agent shown in a heterologous prime-boost immunization protocol
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Department of Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Department of Immunology.
2009 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 30, 4038-4046 p.Article in journal (Refereed) Published
Abstract [en]

In general prime-boost immunization including Mycobacterium bovis bacille Calmette-Guérin (BCG) as a priming agent has been a recent successful strategy in animal models. However, the effects of BCG as a priming vaccine have not been investigated systematically. Thus, we modelled a heterologous prime-boost immunization in mice with BCG administered at the neonatal period and mycobacterial heparin-binding hemagglutinin (HBHA) at adult ages. Mice were challenged with a high dose of BCG (10(7) colony forming units) via intranasal (i.n.) route. We addressed whether the route of administration and addition of adjuvants could be of importance in HBHA-immunizations while animals were primed with BCG. Our results showed that prime-boost immunization induced significantly higher levels of protection in animals compared to the group vaccinated with BCG alone. Most importantly, the levels of protection were comparable between the i.n. and subcutaneous (s.c.) boostings with native (n) HBHA and the coadministration of adjuvant was not necessary. Moreover, priming with BCG improved also the protection promoted by the recombinant form of HBHA, even if to a lower degree to that observed after nHBHA boosting. In general, vaccination with BCG prior to the HBHA administration was found to contribute in two ways: it primed the immune system and provided adjuvant effect. We discuss the several outcomes following neonatal BCG priming and HBHA boosting for better protection against tuberculosis

Place, publisher, year, edition, pages
2009. Vol. 27, no 30, 4038-4046 p.
Keyword [en]
BCG vaccine; Neonates; Heparin-binding hemagglutinin
URN: urn:nbn:se:su:diva-39195DOI: 10.1016/j.vaccine.2009.04.027ISI: 000267581500015OAI: diva2:319025
Available from: 2010-05-12 Created: 2010-05-12 Last updated: 2010-05-31Bibliographically approved
In thesis
1. Mucosal immunity against mycobacterial infection
Open this publication in new window or tab >>Mucosal immunity against mycobacterial infection
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aimed to the identification of immune biomarkers of mycobacterial infection for better diagnosis of tuberculosis (TB) and also focused on new vaccination strategies with a particular emphasis on the immune responses in the respiratory tract using murine models.

Since the lung is the natural habitat for the M. tuberculosis, we reasoned that immune responses detected locally in the lungs would be good correlates of infection (Paper I). Likewise, immune responses induced in the respiratory tract following immunization would be more effective against mycobacterial infection. We showed that cytokines (IL-12, TNF, and IFN-γ) and cytokine receptors (sTNFR1 and sTNFR2) together with specific antibodies in the respiratory tract correlated better with the bacterial burden in the organs. In Paper II, we investigated the role of the BCG vaccination as a priming vaccine in a heterologous prime-boost immunization protocol. The results showed that the neonatal BCG vaccination primed the immune system for a relevant antigen and showed a generalized adjuvant effect. Using this immunization protocol, protective immune responses in the lungs were generated independently of the route used for the booster immunization. In Paper III, We showed that exposure to mycobacterial antigens during the gestational period led to antigen transportation from the mother to the fetus and this resulted in an early priming of the fetal immune system. Immunization with the same antigen during the postnatal life increased antigen-specific recall IFN-γ responses and protection against infection. We examined the role of innate immunity for the induction of acquired immune responses upon immunization with mycobacterial antigens using TLR2 deficient mice (Paper IV). Our data indicated that suboptimal innate immune responses in the TLR2-/- mice might compromise the induction of acquired immune responses.

Overall, the current findings suggested that a better understanding of the mucosal immunity would be useful for the improvement of diagnostic procedures and the development of efficient vaccines against TB.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 93 p.
Mucosal immunity, Vaccination, Diagnosis, Mycobacterial infection
National Category
Immunology in the medical area
Research subject
urn:nbn:se:su:diva-39170 (URN)978-91-7447-081-9 (ISBN)
Public defence
2010-06-18, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: ManuscriptAvailable from: 2010-05-31 Created: 2010-05-12 Last updated: 2010-05-31Bibliographically approved

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