Malaria infections do not compromise vaccine-induced immunity against tuberculosis in mice.
BACKGROUND
Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis.


RESULTS
Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-γ, TNF-α, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL.


CONCLUSIONS
Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas.
Office of Vaccines Research and Review, Center for Biologics Evaluation and Review, USFDA, Bethesda, Maryland, United States of America.
Marcela
M
Parra
Steven C
SC
Derrick
Amy
A
Yang
Jinhua
J
Tian
Kristopher
K
Kolibab
Miranda
M
Oakley
Liyanage P
LP
Perera
William R
WR
Jacobs
Sanjai
S
Kumar
Sheldon L
SL
Morris
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D005260:Female; D008288:Malaria / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D010967:Plasmodium yoelii / Q000472:pathogenicity; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000276:immunology* / Q000469:parasitology
D001500:BCG Vaccine