Co-expression of Interleukin-15 Enhances the Protective Immune Responses Induced by Immunization with a Murine Malaria MVA-Based Vaccine Encoding the Circumsporozoite Protein.
Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Marcela
M
Parra
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Xia
X
Liu
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Steven C
SC
Derrick
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Amy
A
Yang
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, 20852, United States of America.
Alvaro
A
Molina-Cruz
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, 20852, United States of America.
Carolina
C
Barillas-Mury
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Hong
H
Zheng
Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Phuong
P
Thao Pham
Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Martha
M
Sedegah
Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Arnel
A
Belmonte
Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
Dianne D
DD
Litilit
National Cancer Institute, Bethesda, MD, 20892, United States of America.
Thomas A
TA
Waldmann
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Sanjai
S
Kumar
Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD, 20993, United States of America.
Sheldon L
SL
Morris
National Cancer Institute, Bethesda, MD, 20892, United States of America.
Liyanage P
LP
Perera
D000818:Animals; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D019409:Interleukin-15; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan