NDLI: Selected prfA* Mutations in Recombinant Attenuated Listeria monocytogenes Strains Augment Expression of Foreign Immunogens and Enhance Vaccine-Elicited Humoral and Cellular Immune Responses▿

Content Provider	PubMed Central
Author	Yan, Lin Qiu, Jin Chen, Jianbo Bridgett, Ryan-payseur Huang, Dan Wang, Yunqi Rong, Lijun Melton-witt, Jody A. Freitag, Nancy E. Chen, Zheng W.
Abstract	While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes ΔactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes ΔactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes ΔactA vaccine vector. Thus, recombinant attenuated L. monocytogenes ΔactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.
Related Links	http://dx.doi.org/10.1128/iai.00245-08
Ending Page	3450
Page Count	12
Starting Page	3439
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	8
Volume Number	76
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2008-08-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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