Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

Autor: Sean Paul Nuccio, Seung-Joo Lee, Jason P. Mooney, Kristen L. Lokken, Stephen J. McSorley, Minelva R. Nanton, Renée M. Tsolis
Přispěvatelé: Ryan, Edward T
Jazyk: angličtina
Rok vydání: 2015
Předmět:
CD4-Positive T-Lymphocytes
and promotion of well-being
Bacteremia
CD8-Positive T-Lymphocytes
Inbred C57BL
Immune tolerance
Mice
2.1 Biological and endogenous factors
2.2 Factors relating to the physical environment
Cytotoxic T cell
Aetiology
Vaccines
Medical And Health Sciences
lcsh:Public aspects of medicine
Bacterial
Salmonella vaccine
Biological Sciences
Foodborne Illness
Acquired immune system
Antibodies
Bacterial
Vaccination
Infectious Diseases
3.4 Vaccines
Salmonella Infections
Female
Infection
Plasmodium yoelii
Biotechnology
Research Article
lcsh:Arctic medicine. Tropical medicine
Salmonella Vaccines
lcsh:RC955-962
Biology
Vaccines
Attenuated
Antibodies
Vaccine Related
Rare Diseases
Malaria Vaccine
Biodefense
Tropical Medicine
parasitic diseases
medicine
Immune Tolerance
Animals
Salmonella Infections
Animal
Animal
Prevention
Public Health
Environmental and Occupational Health
Inbred CBA
Plasmodium falciparum
lcsh:RA1-1270
Prevention of disease and conditions
medicine.disease
biology.organism_classification
Virology
Malaria
Vector-Borne Diseases
Mice
Inbred C57BL
Disease Models
Animal
Emerging Infectious Diseases
Orphan Drug
Good Health and Well Being
Attenuated
Immunology
Disease Models
Mice
Inbred CBA
Immunization
Zdroj: PLoS Neglected Tropical Diseases, Vol 9, Iss 9, p e0004027 (2015)
PLoS neglected tropical diseases, vol 9, iss 9
Mooney, JP; Lee, SJ; Lokken, KL; Nanton, MR; Nuccio, SP; McSorley, SJ; et al.(2015). Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria. PLoS Neglected Tropical Diseases, 9(9), e0004027. doi: 10.1371/journal.pntd.0004027. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/9665n4fq
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
DOI: 10.1371/journal.pntd.0004027.
Popis: In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonlethal malaria parasite Plasmodium yoelii 17XNL exhibited a profound loss of protective immunity to NTS, but vaccine-mediated protection was restored after resolution of malaria. Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. Blockade of IL-10 restored protection against S. Typhimurium, without restoring CD4 T cell effector function. Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-γ production by vaccine-induced memory CD4 T cells but was not sufficient to restore protection. Together, these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms, and suggest that in the setting of acute malaria, protection against NTS mediated by live vaccines may be interrupted.
Author Summary In children, malaria is a predisposing factor for invasive bacterial infections with non-typhoidal Salmonella (NTS) serovars, a frequent cause of morbidity and mortality in sub-Saharan Africa. Since development of vaccines against NTS has been proposed as a strategy to protect African children against disseminated NTS infection, we interrogated the effect of malaria on vaccine-induced memory responses to NTS. Our results from a mouse infection model show that infection with malaria parasites temporarily suspends protective immunity conferred by a live, attenuated vaccine and suppresses adaptive immune responses to NTS that are mediated by T cells. These results suggest that in the setting of acute malaria, live attenuated NTS vaccines may lose their effectiveness.
Databáze: OpenAIRE
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