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Induction of Protective Immunity to Listeria monocytogenes in Neonates¹

Tobias R. Kollmann^2,*,,, Brian Reikie, Darren Blimkie, Sing Sing Way^*,, Adeline M. Hajjar^*, Kiea Arispe^*, Angela Shaulov^* and Christopher B. Wilson^*,

^* Departments of Pediatrics and Immunology, University of Washington School of Medicine, Seattle, WA 98195; and Department of Pediatrics, Division of Infectious and Immunological Diseases, British Columbia Children’s and Women’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada

Neonates suffer unduly from infections and also respond suboptimally to most commonly used vaccines. However, a CD8 T cell response can be elicited in neonates if the Ag is introduced into the cytoplasm of APCs. Listeria monocytogenes (Lm) targets the cytoplasm of APC and is a strong CD8 and CD4 Th1-promoting vaccine vehicle in adult mice. We hypothesized that an attenuated strain of Lm would be safe and induce long-lasting protective immunity, even in neonates. We found that neonatal mice immunized only once with the attenuated strain actA-Lm developed robust primary and secondary CD8 and CD4 Th1 responses and were fully protected from lethal challenge with virulent wild-type Lm without the need for a booster immunization. Furthermore, actA-Lm expressing a heterologous recombinant Ag induced a strong CD8 and Th1 memory response to that Ag. Based on these data, we propose that actA-Lm or derivatives thereof might serve as a vaccine vehicle for neonatal immunization.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HD049826 (KO8 to T.R.K), HD043376 (K12 to T.R.K.), HL069503 (RO1 to A.M.H.), and HD018184 (RO1 to C.B.W.). The research of T.R.K. is supported in part by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund.

² Address correspondence and reprint requests to Dr. Tobias R. Kollmann, Department of Pediatrics, Division of Infectious and Immunological Diseases, Children’s Hospital of British Columbia, University of British Columbia, Child and Family Research Institute Room 304, 950 West 28th Avenue, Vancouver, British Columbia, Canada. E-mail address: tkollmann{at}cw.bc.ca

³ Abbreviations used in this paper: Lm, Listeria monocytogenes; WT, wild type.

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