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

Abstract

Immune senescence in the elderly results in decreased immunity with a concomitant increase in susceptibility to infection and diminished efficacy of vaccination. Nonhuman primate (NHP) models have proven critical for testing of vaccines and therapeutics in the general population, but a model using old animals has not been established. Towards that end, immunity to LcrV, a protective antigen 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 antibody 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 antigen was also tested in mice and, as expected, age-associated loss of immunity was seen; older animals responded with lower titer antibodies 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.

Sm‐p80–Based DNA Vaccine Provides Baboons with Levels of Protection againstSchistosomamansoniInfection Comparable to Those Achieved by the Irradiated Cercarial Vaccine

“…IgG3, IgG4 and IgE responses were not detectable. Similarly in vaccination studies using Plague antigen LcrV in baboons [38], and in our previous studies with Sm-p80-pcDNA3 [14], IgG3 and IgG4 were found to be under the detection limits. However it is possible that the non-detection of IgG3 and IgG4 (and IgE) could be due to the poor cross-reactivity of human reagents being used for the detection of baboon antibody subtypes since no host-specific secondary antibodies from nonhuman primate origin are available for these subtypes [14].…”

The Effects of Age and Cytomegalovirus on Markers of Inflammation and Lymphocyte Populations in Captive Baboons

“…Blood was collected from 33 females and 5 males ranging in age from 6 to 26 years old with a mean age of 14 years. It is estimated that this baboon age range would correspond to a human age range of approximately 18–78 years old [18], [19]. The average lifespan of baboons in captivity is approximately 21 years of age [20] and our population included 14 young adult (<13 years), 14 middle aged (13–17 years), and 10 aged baboons (>17 years).…”

Protecting against plague: towards a next-generation vaccine

“…The range of species in which the V antigen or F1/V vaccine combination has been evaluated is constantly growing, and now includes data generated in Old World non-human primates [71][72][73][74][75][76][77][78], as evidence is collected to achieve regulatory approval. The immunogenicity and efficacy data reported to date from these models are summarized in Table 2.…”