ABSTRACT
Development of cattle vaccines against bovine tuberculosis is a GB research priority. Recently, it has been shown that formalin-killed Bacille Calmette-Guérin (BCG) delivered with the liposomal adjuvant NAX687 imparted significant protection against Mycobacterium bovis infection in the guinea pig aerosol infection model. Extending these studies, we inoculated calves with live BCG, formalin-killed BCG and formalin-killed BCG formulated in NAX687. Live and killed BCG vaccine formulations induced primary effector T-cell populations comparably, both killed BCG formulations also induced potent humoral immune responses. In contrast, live BCG generated enhanced central memory responses against the protective antigen Ag85A whilst killed BCG-induced such responses only poorly. However, the poor capacity of killed BCG to generate central memory could be partially overcome by formulation with NAX687. Measurement of central memory responses induced by TB vaccine candidates in cattle may provide a useful correlate of protection and warrants further investigation in challenge experiments.
Subject(s)
BCG Vaccine/immunology , Cattle Diseases/prevention & control , Immunologic Memory , Mycobacterium bovis/immunology , Tuberculosis/veterinary , Adjuvants, Immunologic/administration & dosage , Animals , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Cattle , Cattle Diseases/immunology , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Interferon-gamma/blood , Interferon-gamma/metabolism , T-Lymphocytes/immunology , Tuberculosis/immunology , Tuberculosis/prevention & control , Vaccines, Attenuated/immunology , Vaccines, Inactivated/immunologyABSTRACT
The development of safe and effective vaccines for avian influenza viruses is a priority for pandemic preparedness. Adjuvants improve the efficacy of vaccines and may allow antigen sparing during a pandemic. We have previously shown that influenza virus-like particles (VLPs) comprised of HA, NA, and M1 proteins represent a candidate vaccine for avian influenza H9N2 virus [Pushko P, Tumpey TM, Fang Bu, Knell J, Robinson R, Smith G. Influenza virus-like particles comprised of the HA, NA, and M1 proteins of H9N2 influenza virus induce protective immune responses in BALB/c mice. Vaccine 2005;23(50):5751-9]. In this study, an H9N2 VLP vaccine and recombinant HA (rH9) vaccine were evaluated in three animal models. The H9N2 VLP vaccine protected mice and ferrets from challenge with A/Hong Kong/1073/99 (H9N2) virus. Novasome adjuvant improved immunogenicity and protection. Positive effect of the adjuvant was also detected using the rH9 vaccine. The results have implications for the development of safe and effective vaccines for avian influenza viruses with pandemic potential.
Subject(s)
Adjuvants, Immunologic/pharmacology , Influenza A Virus, H9N2 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Virosomes/immunology , Animals , Antibodies, Viral/blood , Body Weight , Disease Models, Animal , Female , Ferrets , Hemagglutination Inhibition Tests , Humans , Influenza, Human/immunology , Male , Mice , Mice, Inbred BALB C , Microscopy, Electron, Transmission , Rats , Spodoptera/cytology , Vaccines, Synthetic/immunology , Virosomes/ultrastructureABSTRACT
The only vaccine currently available for the prevention of tuberculosis in man is a live attenuated vaccine, bacille Calmette-Guerin (BCG), derived from Mycobacterium bovis. Concerns over the lack of the universal efficacy and safety of BCG have resulted in efforts to develop a new generation of TB vaccines. Historically, killed whole-cell preparations of mycobacteria have been ineffective vaccines. We revisited the potential of killed whole-cell vaccines by comparing their efficacy with live BCG Pasteur in a guinea pig challenge model. BCG Pasteur was inactivated with a low concentration of formalin and showed to be non-viable in culture or severe combined immunodeficient mice. Formalin-inactivated BCG was mixed with non-phospholipid liposome adjuvants (Novasomes) and administered to guinea pigs as a single subcutaneous inoculation. All formulations were well tolerated and one conferred a significant survival advantage against lethal aerogenic challenge with M. bovis.
