Cutting Edge: Subunit Booster Vaccination Confers Sterilizing Immunity against Liver-Stage Malaria in Mice Initially Primed with a Weight-Normalized Dose of Radiation-Attenuated Sporozoites

Radiation-attenuated sporozoite (RAS) vaccination offers hope for global malaria control through induction of protective liver-stage-specific memory CD8 T cells. Effective RAS vaccination regimens exist; however, widespread implementation remains unfeasible. A key difficulty resides in the need to a...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2021-12, Vol.207 (11), p.2631-2635
Main Authors: Lefebvre, Mitchell N, Drewry, Lisa L, Pewe, Lecia L, Hancox, Lisa S, Reyes-Sandoval, Arturo, Harty, John T
Format: Article
Language:English
Subjects:
Animals
Immunization
Liver Diseases - immunology
Malaria - immunology
Malaria Vaccines - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Sporozoites - immunology
Vaccination
Vaccines, Attenuated - immunology
Vaccines, Subunit - immunology
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Summary:Radiation-attenuated sporozoite (RAS) vaccination offers hope for global malaria control through induction of protective liver-stage-specific memory CD8 T cells. Effective RAS vaccination regimens exist; however, widespread implementation remains unfeasible. A key difficulty resides in the need to administer three or more doses i.v. to achieve sufficient immunity. Strategies to reduce the number of RAS doses are therefore desirable. Here we used mice to model human immune responses to a single, suboptimal weight-normalized RAS dose administered i.v. followed by subunit vaccination to amplify liver-stage-specific memory CD8 T cells. RAS+subunit prime-boost regimens increased the numbers of liver-stage-specific memory CD8 T cells to a level greater than is present after one RAS vaccination. Both i.v. and i.m. subunit vaccine delivery induced immunity in mice, and many vaccinated mice completely cleared liver infection. These findings are particularly relevant to human vaccine development because RAS+subunit prime-boost vaccination would reduce the logistical challenges of multiple RAS-only immunizations.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2100818