Immune Responses Induced in Cattle by Vaccination with a Recombinant Adenovirus Expressing Mycobacterial Antigen 85A and Mycobacterium bovis BCG

Division of Infectious Diseases, McMaster University, Hamilton, Ontario, Canada
Infection and Immunity (Impact Factor: 3.73). 03/2006; 74(2):1416-8. DOI: 10.1128/IAI.74.2.1416-1418.2006
Source: PubMed


Cattle were vaccinated with an adenovirus expressing the mycobacterial antigen 85A (rAd85A), with Mycobacterium bovis BCG followed by rAd85A heterologous boosting, or with rAd85A followed by BCG boosting. BCG/rAd85A resulted in the highest
direct gamma interferon responses. Cultured enzyme-linked immunospot assay analysis demonstrated that memory responses were
induced by all three protocols but were strongest after BCG/rAd85A and rAd85A/BCG vaccination.

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    • "After eight weeks, the proportion of T EFF relative to effector memory CD8 + T cells (T EM ) was similar for all three vectors, with a majority adopting a T EM phenotype as observed previously [30] [44]. Few previous studies have assessed the kinetics of vaccine antigen specific T cell responses after adenovirus vector administration in cattle [43], and none to our knowledge have compared the immunogenicity of vectors derived from members of different human adenovirus species. In the current study, IFN-␥ + CD8 + and CD4 + T cell responses were highest two weeks post-vaccination (Fig. 5), similar to observations in mice at the lower 10 6 ifu dose (Fig. 3C). "
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    ABSTRACT: Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ(+) CD8(+) T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5. Copyright © 2015. Published by Elsevier Ltd.
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    • "As a matter of fact, numerous studies have already shown that BCG induces a significant level of protection against development of lesions in animals vaccinated and challenged with virulent strains [9], [10], [11], [12], [13]. Subcutaneous and oral administrations of BCG, the use of BCG in a lipid matrix, and different BCG strains have shown protection [14], [15]. It has been shown that: low doses of BCG [103–106 colony forming units (CFU)] induce better protection than higher doses [5], pre-exposure to environmental Mycobacterium can negatively affect vaccine efficacy [16], vaccination of neonatal calves induced a higher level of immunity than that observed in calves vaccinated at 5–6 months of age [11], [12], [17], and that boosting with culture filtrate proteins (CFP) of M. bovis, plus adjuvant induce a better Th1 response. "
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    ABSTRACT: "Test-and-slaughter" has been successful in industrialized countries to control and eradicate tuberculosis from cattle; however, this strategy is too expensive for developing nations, where the prevalence is especially high. Vaccination with the Calmette-Guérin (BCG) strain has been shown to protect against the development of lesions in vaccinated animals: mouse, cattle and wildlife species. In this study, the immune response and the pathology of vaccinated (BCG-prime and BCG prime-CFP-boosted) and unvaccinated (controls) calves were evaluated under experimental settings. A 10(6) CFU dose of the BCG strain was inoculated subcutaneously on the neck to two groups of ten animas each. Thirty days after vaccination, one of the vaccinated groups was boosted with an M. bovis culture filtrate protein (CFP). Three months after vaccination, the three groups of animals were challenged with 5×10(5) CFU via intranasal by aerosol with a field strain of M. bovis. The immune response was monitored throughout the study. Protection was assessed based on immune response (IFN-g release) prechallenge, presence of visible lesions in lymph nodes and lungs at slaughter, and presence of bacilli in lymph nodes and lung samples in histological analysis. Vaccinated cattle, either with the BCG alone or with BCG and boosted with CFP showed higher IFN-g response, fewer lesions, and fewer bacilli per lesion than unvaccinated controls after challenge. Animals with low levels of IFN-g postvaccine-prechallenge showed more lesions than animals with high levels. Results from this study support the argument that vaccination could be incorporated into control programs to reduce the incidence of TB in cattle in countries with high prevalence.
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    • "This represents yet another important difference between murine and guinea pig models as in our present study we have shown both intranasal and intramuscular boosting is effective in protracting the survival of BCG-primed guinea pigs although intranasal boosting appears to be more potent than intramuscular boosting (greater than 60% survival by i.n boosting vs 40% by i.m boosting at 74 weeks post-challenge). In fact, this finding is consistent with our recent cattle studies where parenteral AdAg85A boosting was found to be effective not only in enhancing memory T cell responses triggered by BCG priming [15] but also in enhancing protection from pulmonary tuberculosis (unpublished study). Together these findings from both guinea pig and bovine models raise the hope that parenteral boosting with virus-based TB vaccine will be sufficient to enhance protective immunity in previously BCG-vaccinated humans. "
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