Exposure to Mycobacterium avium Decreases the Protective Effect of the DNA Vaccine pVAXhsp65 Against Mycobacterium tuberculosis‐Induced Inflammation of the Pulmonary Parenchyma

Abstract

This work investigated the effect of previous Mycobacterium avium exposure on the protective ability of the DNA vaccine pVAXhsp65 against inflammation in the pulmonary parenchyma. BALB/c mice were presensitized with heat‐killed M. avium and then immunized with three doses of pVAXhsp65 prior to challenge with Mycobacterium tuberculosis. M. avium sensitization induced high levels of spontaneous IL‐5 production that were concomitant with a positive delayed‐type hypersensitivity reaction; antigen‐specific IFN‐γ production was also observed upon splenocyte stimulation. Prior exposure to M. avium resulted in altered cytokine and antibody production induced by immunization with pVAXhsp65; instead of a Th1 response, vaccinated mice previously exposed to M. avium developed a strong Th2 response. This switch to a Th2 response coincided with the loss of the anti‐inflammatory effect of pVAXhsp65 vaccination previously observed in the pulmonary parenchyma of mice infected with M. tuberculosis. These results suggest that exposure to environmental mycobacteria can modulate immune responses induced by mycobacterial vaccines other than bacillus Calmette–Guérin.

Pre-treatment with Mycobacterium avium-derived lipids reduces the macrophage response to interferon γ in BCG-vaccinated mice

“…The exposure to environmental mycobacteria is prevalent in countries with a low BCG vaccination efficacy (Fine, 1989). Further studies demonstrated that exposure to environmental mycobacteria prior to BCG vaccination could mask the effects of BCG (Howard et al , 2002; Martins et al , 2011). In mice that were not vaccinated with BCG, high levels of M. avium affected the host immune response by upregulating CD95 expression in T cells, which suppressed T-cell–macrophage interactions, promoted IL-10 production and reduced the secretion of IL-12, IL-8 and CCL5 (Zhong et al , 2003; Roger & Bermudez, 2001; Wagner et al , 2002).…”

IFN‐γ against the 38‐kDa antigen of Mycobacterium tuberculosis discriminates pulmonary tuberculosis from infection and infection from exposure: evidence from a study of human population in a high endemic setting

“…There are two cross‐sectional studies, two from Brazil , and one from Mexico that looked into IFN‐γ responses against the 38‐kDa protein in TB patients. Immune responses to Mtb antigens are influenced, among others, by genetics of the host , strain of Mtb , and environmental mycobacteria . However, to our knowledge, there is no information on T‐cell responses (cytokines production) against this antigen in human population in Africa, a high TB endemic setting.…”