An Inter-Laboratory Retrospective Analysis of Immunotoxicological Endpoints in Non-Human Primates: T-Cell-Dependent Antibody Responses

  • Publication Date :
  • Publication Type : Journal Article
  • Author(s) : Lebrec H, Cowan L, Lagrou M, Krejsa C, Neradilek MB, Polissar NL, Black L, Bussiere J
  • Journal Name : Journal of Immunotoxicology

Journal of Immunotoxicology. 2011;8(3):238-250

Abstract: The Immunotoxicology Technical Committee of HESI sponsored a retrospective analysis of T-cell-dependent antibody responses in non-human primates (NHP). Antibody responses to keyhole limpet hemocyanin (KLH), tetanus toxoid (TT), and/or sheep red blood cells (SRBC) in 178 NHP (from 8 sponsors, 13 testing sites, 30 studies) were statistically analyzed. Rates of positive or negative anti-KLH, -TT, and -SRBC primary and secondary IgM and IgG responses were compared. The influence of gender, country of origin, and previous immunization with a different antigen on response rate and kinetics of anti-KLH and anti-TT responses were analyzed. In addition, the magnitude of the antibody responses and the impact of the above-mentioned factors were analyzed. In addition, based upon the inter-individual variability of the peak response values, power calculations were conducted. The analysis demonstrated that the rates of positive responses were similar between the two genders, were high for KLH, SRBC, and TT challenges by 21 days following immunization (87, 100, and 84%, respectively, for IgGs) and did not include statistically significant differences based on NHP country of origin. Mean peak secondary responses were greater than peak primary responses; the magnitude of the response to KLH was increased by incomplete Freund’s adjuvant (IFA). Gender had little effect on the magnitude and variability of these responses. KLH and TT were associated with similar inter-animal variability, whereas in some situations KLH responses were less variable than responses to SRBC. The data suggested that inter-animal variability with KLH was similar with or without IFA. Power analysis illustrated that animal group sizes of typical standard toxicology studies (generally ≤ 4/sex) are likely to detect only fairly large treatment effects. However, combining males and females, when appropriate, will improve the power: an N of 8 to 12 could detect ≤ 3.1-fold differences in anti-KLH IgG responses.

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