A Recombinant Bacillus Calmette-Guérin (BCG) vaccine promotes protective humoral immunity against the human respiratory syncytial virus
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1
Millennium Institute on Immunology and Immunotherapy. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile
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2
Facultad de Medicina, Pontificia Universidad Católica de Chile, Departamento de Inmunología Clínica y Reumatología, Chile
Human respiratory syncytial virus (hRSV) is the leading cause of hospitalizations due to acute respiratory tract infections in children younger than two years. HRSV causes a wide variety of symptoms, which are associated with upper and lower respiratory tract inflammation (i.e. bronchiolitis and pneumonia). Currently, there are no commercially available vaccines for prevention of hRSV infections in susceptible individuals. Therefore, the development of vaccine prototypes against this virus is a major challenge and a priority worldwide. HRSV induces a Th2-type inflammatory immune pathology that is thought to be controlled by the induction of a balanced antiviral Th1-type response. Along this line, the tuberculosis vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a recognized inducer of Th1 immunity. Previous data of our laboratory showed that immunization with a recombinant BCG expressing the hRSV nucleoprotein induces the expansion of hRSV-specific IFN-γ secreting T cells, which are able to prevent pathology and decrease viral loads in the lungs. In order to continue characterizing the protection given by rBCG-N, we analyze serum samples obtained from immunized and challenge mice and evaluate the generation of specific anti-hRSV protein antibodies as well as their isotype and their effector capacities. After viral challenge and compared to controls, BCG-N immunized mice showed a significant increase in the level of IgG specific against the virus, which included antibodies specific for the hRSV fusion (F), attachment (G) and N proteins. Furthermore, at day 14 post infection we analyzed the isotype of hRSV-specific immunoglobulins in both control and BCG-N-immunized mice. Importantly, BCG-N immunized mice showed a predominance of IgG2a isotype, with lower levels of IgG1, suggesting that type 1 helper T cells (Th1) may provide stimulation to B cells to enhance IgG2a production. Moreover, we performed functional characterization of the antibody repertoire generated by BCG-N immunization, including the evaluation of neutralizing and complement-fixing capacities. Among others, pre-incubation of a GFP-encoding hRSV with sera of control and immunized mice showed that only sera collected from BCG-N immunized mice were capable of directly neutralize infectious virus particles. Finally, we evaluated the ability of serum antibodies to bind C1q peptide. As expected, we observed that antibodies collected from immunized mice bound C1q peptide in a higher proportion than antibodies of control mice, suggesting that these antibodies fix complement efficiently. Altogether, these results suggest that BCG-N vaccine promotes the acquisition of an antiviral humoral immune response that exploit a variety of effector mechanisms to restrain hRSV dissemination and pathology.
Acknowledgements
This work was supported by funding from the Millennium Institute on Immunology and Immunotherapy from Chile (P09/016-F to AMK). FONDECYT no 1070352, FONDECYT no 1050979, FONDECYT no 1040349, FONDECYT no 1100926, FONDECYT no 1110397, FONDECYT no 1100971, FONDECYT no 1110604, FONDECYT postdoctorado no 3140455 and BMRC CTU06.
Keywords:
HRSV,
Vaccines,
Antibodies,
B cells,
Complement System Proteins
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Infectious and parasitic diseases
Citation:
Rivera
CA,
Díaz
RA,
Céspedes
PF,
Bueno
SM and
Kalergis
AM
(2015). A Recombinant Bacillus Calmette-Guérin (BCG) vaccine promotes protective humoral immunity against the human respiratory syncytial virus.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00177
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Received:
04 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
PhD. Alexis M Kalergis, Millennium Institute on Immunology and Immunotherapy. Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, santiago, santiago, Chile, akalergis@bio.puc.cl