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. 2005 Aug;73(8):5039-47.
doi: 10.1128/IAI.73.8.5039-5047.2005.

Scrub typhus vaccine candidate Kp r56 induces humoral and cellular immune responses in cynomolgus monkeys

Suchismita Chattopadhyay  1 , Ju Jiang, Teik-Chye Chan, T Scott Manetz, Chien-Chung Chao, Wei-Mei Ching, Allen L Richards
Affiliations

Scrub typhus vaccine candidate Kp r56 induces humoral and cellular immune responses in cynomolgus monkeys

Suchismita Chattopadhyay et al. Infect Immun. 2005 Aug.

Abstract

A truncated recombinant 56-kDa outer membrane protein of the Karp strain of Orientia tsutsugamushi (Kp r56) was evaluated in cynomolgus monkeys (Macaca fascicularis) for immunogenicity and safety as a vaccine candidate for the prevention of scrub typhus. This recombinant antigen induced strong humoral and cellular immune responses in two monkeys and was found to be well tolerated. Antigen-specific immunoglobulin M (IgM) and IgG were produced to almost maximal levels within 1 week of a single immunization. Peripheral blood mononuclear cells from vaccinated animals showed an induction of antigen-specific proliferation and gamma interferon production. The Kp r56 was not as efficient as infection with live organisms in preventing reinfection but was able to reduce the inflammation produced at the site of challenge. This report describes the results of the first systematic study of the immunogenicity of a recombinant scrub typhus vaccine candidate in a nonhuman primate model.

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Figures

FIG. 1.
FIG. 1.
Antibody (IgM and IgG) titers in serum of cynomolgus monkeys after infection and challenge with O. tsutsugamushi and vaccination with Kp r56.
FIG. 2.
FIG. 2.
In vitro proliferation of PBMC from cynomolgus monkeys in response to infection with O. tsutsugamushi Karp. Animals 1 and 3, respectively, were infected with 106 (A) and 102 (B) MuLD50 and challenged after 8 weeks with 106 MuLD50.
FIG. 3.
FIG. 3.
In vitro production of IFN-γ by PBMC of cynomolgus monkeys infected and challenged with O. tsutsugamushi Karp. Monkeys (1 and 3) were infected at week 0 with 106 (A) and 102 (B) MuLD50, respectively, and challenged after week 8 with 106 MuLD50 of O. tsutsugamushi Karp.
FIG. 4.
FIG. 4.
In vitro proliferation of PBMC from two cynomolgus monkeys in response to vaccination and challenge with O. tsutsugamushi Karp. Animals 5 and 6 were vaccinated with Kp r56 and challenged after 4 weeks with 106 MuLD50 of O. tsutsugamushi Karp.
FIG. 5.
FIG. 5.
In vitro production of IFN-γ by PBMC of two cynomolgus monkeys vaccinated with Kp r56 and challenged with O. tsutsugamushi Karp. Monkeys 5 and 6 were vaccinated with Kp r56 and challenged 4 weeks later with 106 MuLD50 of O. tsutsugamushi Karp.
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