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An Age-Old Paradigm Challenged: Old Baboons Generate Vigorous Humoral Immune Responses to LcrV, A Plague Antigen¹

Sue Stacy^*,, Amanda Pasquali^*, Valerie L. Sexton, Angelene M. Cantwell, Ellen Kraig^2,*, and Peter H. Dube^,

^* Department of Cellular and Structural Biology, Department of Microbiology and Immunology, and Barshop Center for Longevity Studies, University of Texas Health Science Center, San Antonio, TX 78229

Immune senescence in the elderly results in decreased immunity with a concomitant increase in susceptibility to infection and diminished efficacy of vaccination. Nonhuman primate models have proven critical for testing of vaccines and therapeutics in the general population, but a model using old animals has not been established. Toward that end, immunity to LcrV, a protective Ag from Yersinia pestis, was tested in young and old baboons. Surprisingly, there was no age-associated loss in immune competence; LcrV elicited high-titer, protective Ab responses in the older individuals. The primary responses in the younger baboons were lower, but they did show boosting upon secondary immunization to the levels achieved in the old animals. The LcrV Ag was also tested in mice and, as expected, age-associated loss of immunity was seen; older animals responded with lower-titer Abs and, as a result, were more susceptible to Yersinia challenge. Thus, although age-related loss in immune function has been observed in humans, rodents, and some nonhuman primates, baboons appear to be unusual; they age without losing immune competence.

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 funding from the Southwest National Primate Center (pilot study Grant P51 RR13986), the National Institute on Aging (R03AG22675 to S.S.), and a University of Texas Health Science Center, San Antonio Presidential Research Enhancement Fund grant.

² Address correspondence and reprint requests to Dr. Ellen Kraig, Cellular and Structural Biology MC 7762, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229. E-mail address: kraig{at}uthscsa.edu

³ Abbreviations used in this paper: NHP, Nonhuman primate; TTFC, Tetanus toxoid fragment C.