Effect of Chronic Social Stress on Prenatal Transfer of Antitetanus Immunity in Captive Breeding Rhesus Macaques (Macaca mulatta)

Abstract

Because tetanus can cause significant morbidity and mortality in NHP, colonywide vaccination with tetanus toxoid is recommended for outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. Maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. However, historical colony data from the Yerkes National Primate Research Center show a higher incidence of tetanus among infants (≤ 6 mo old) born to subordinate dams. Whether this higher incidence of infantile tetanus is due to a higher incidence of trauma among subordinate animals or is a stress-induced impairment of maternal antibody protection is unknown. Studies in other NHP species suggest that chronic exposure to social stressors interferes with the receptor-mediated transplacental transfer of IgG. Therefore, the primary aim of this study was to determine whether chronic stress associated with social subordination impairs prenatal transfer of antitetanus immunity in breeding female rhesus macaques. Subjects included 26 high- and 26 low-ranking adult female rhesus macaques that were nearly 5 or 10 y after their initial immunization and their nonimmunized infants. We hypothesized that infants born to subordinate dams that were nearly 10 y after immunization would have the lowest infant-to-dam antibody ratios and thus would be at greatest risk for infection. Results revealed no significant intergroup differences in infant antitetanus IgG levels. However, infant-to-dam IgG ratios against tetanus were significantly lower among subordinate animals compared with dominant macaques, after accounting for the number of years since the dam's initial vaccination. In addition, higher maternal hair cortisol levels predicted lower infantto-dam tetanus toxoid IgG ratios. Together, these findings suggest that chronic social stress in female rhesus macaques may hamper the prenatal transfer of antitetanus immunity to offspring.

Figure 1.

Antitetanus IgG levels in dams. (A) Antitetanus IgG levels were significantly lower in high-ranking dams than their low-ranking counterparts. (B) Antitetanus IgG levels were significantly higher among dams at 5 y after immunization compared with dams at 10 y after immunization, regardless of social rank. (C) Antitetanus antibody levels did not differ between low- and high-ranking dams at 5 y after immunization (that is, low-5 compared with high-5); however, TT IgG levels differed significantly between low- and high-ranking dams at 10 y after immunization (that is, low-10 compared with high-10). Different letters indicate significantly (P < 0.05) different values. Data are expressed as means ± 95% confidence intervals.

Figure 2.

Antitetanus IgG levels in infants. Antitetanus IgG levels among infants did not differ depending on whether their dams were low- or high-ranking or on the dam's time past immunization (that is, 5 or 10 y). Data are expressed as means ± 95% confidence intervals.

Figure 3.

Relationship between antitetanus IgG levels in dams and infants. A strong positive relationship was found between infant and dam TT IgG levels (R₅₀ = 0.63, P < 0.0001). The TT IgG levels of 2 of the 15 infants in the high-5 group and 3 of the 14 infants in the low-5 group had TT IgG levels above the 500-U/mL positive–negative threshold (horizontal line), whereas the titers of all of the infants in the high- and low-10 groups were below 500 U/mL.

Figure 4.

Infant-to-dam ratio of antitetanus IgG levels. (A) The ratio of infant-to-dam TT IgG levels were significantly lower among low-ranking infant and maternal pairs than that observed for their more dominant counterparts. (B) The mean ratio of antitetanus IgG levels among infant and maternal pairs 5 y after immunization was significantly lower than those 10 y afterward, regardless of social rank. (C) Analyses of the same data by 4 experimental group revealed that the mean ratio of infant-to-dam TT IgG levels was significantly higher among high-ranking infant and maternal pairs at 10-y after immunization compared with lower-ranking animals at 5 y afterward. Nearly significant group differences were found when comparing low-10 with high-10 (P = 0.07) and high-5 with high-10 (P = 0.0501). Different letters indicate significantly (P < 0.05) different values. Data are expressed as means ± 95% confidence intervals.

Figure 5.

Infant antitetanus IgG group means as a percentage of dam group means. (A) Overall, the TT IgG level among the infants in each experimental group was a small percentage (5% to 33%) of the respective dam TT IgG levels. In addition, gross visual examination of these data suggests a cutoff value for prenatal transfer of TT-specific IgG to offspring. (B) Maternal TT IgG levels were inversely related to the ratio of infant-to-dam TT IgG levels (R₅₀ = –0.68, P < 0.0001), suggesting that higher maternal TT IgG levels are associated with less efficient transfer of TT-specific maternal antibodies to the fetus during late gestation.

Figure 6.

Relationship between maternal hair cortisol and antitetanus IgG levels. (A) Dam hair cortisol was positively correlated with dam TT IgG levels (R₅₀₎ = 0.33, P < 0.05). (B) Dam hair cortisol was negatively correlated with the ratio of infant-to-dam TT IgG levels (R₅₀ = –0.29, P < 0.05).