Gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial Ag85B

Autor: Judd E. Shellito, Weitao Huang, Carol M. Mason, Alistair J. Ramsay, Hamada F. Rady, Guixiang Dai
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
T-Lymphocytes
0302 clinical medicine
Vaccines
DNA
Administration
Mucosal
030212 general & internal medicine
Tuberculosis Vaccines
Lung
Drug Carriers
Mice
Inbred BALB C
Vaccines
Synthetic
biology
Immunogenicity
Vector vaccine
Recombinant Proteins
Treatment Outcome
Infectious Diseases
medicine.anatomical_structure
Molecular Medicine
Female
Tuberculosis
T cell
Genetic Vectors
Article
Adenoviridae
DNA vaccination
Mycobacterium tuberculosis
03 medical and health sciences
Immune system
Bacterial Proteins
Antigen
medicine
Animals
Humans
Antigens
Bacterial
General Veterinary
General Immunology and Microbiology
business.industry
Public Health
Environmental and Occupational Health
medicine.disease
biology.organism_classification
Virology
Bacterial Load
Disease Models
Animal
030104 developmental biology
Immunology
business
Acyltransferases
Zdroj: Vaccine. 34:6267-6275
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2016.10.065
Popis: Tuberculosis remains a major public health hazard worldwide, with neonates and young infants potentially more susceptible to infection than adults. BCG, the only vaccine currently available, provides some protection against tuberculous meningitis in children but variable efficacy in adults, and is not safe to use in immune compromised individuals. A safe and effective vaccine that could be given early in life, and that could also potentiate subsequent booster immunization, would represent a significant advance. To test this proposition, we have generated gene-based vaccine vectors expressing Ag85B from Mycobacterium tuberculosis (Mtb) and designed experiments to test their immunogenicity and protective efficacy particularly when given in heterologous prime-boost combination, with the initial DNA vaccine component given soon after birth. Intradermal delivery of DNA vaccines elicited Th1-based immune responses against Ag85B in neonatal mice but did not protect them from subsequent aerosol challenge with virulent Mtb H37Rv. Recombinant adenovirus vectors encoding Ag85B, given via the intranasal route at six weeks of age, generated moderate immune responses and were poorly protective. However, neonatal DNA priming following by mucosal boosting with recombinant adenovirus generated strong immune responses, as evidenced by strong Ag85B-specific CD4+ and CD8+ T cell responses, both in the lung-associated lymph nodes and the spleen, by the quality of these responding cells (assessed by their capacity to secrete multiple antimicrobial factors), and by improved protection, as indicated by reduced bacterial burden in the lungs following pulmonary TB challenge. These results suggest that neonatal immunization with gene-based vaccines may create a favorable immunological environment that potentiates the pulmonary mucosal boosting effects of a subsequent heterologous vector vaccine encoding the same antigen. Our data indicate that immunization early in life with mycobacterial antigens in an appropriate vaccine setting can prime for protective immunity against Mtb.
Databáze: OpenAIRE
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