Modified Dose Efficacy Trial of a Canine Distemper-Measles Vaccine for Use in Rhesus Macaques (Macaca mulatta)

Abstract

Measles virus causes a highly infectious disease in NHP. Clinical signs range from asymptomatic to fatal, although measles virus is most well-known for its characteristic generalized maculopapular rash. Along with appropriate quarantine practices, restricted human access, and appropriate personal protective equipment, vaccines are used to combat the risk of infection. The canine distemper-measles vaccine (CDMV), administered at the manufacturer's standard dose (1.0 mL IM), has been shown to be effective against clinical measles disease in rhesus macaques (Macaca mulatta). The goal of the current study was to test whether doses smaller than the manufacturer's recommended dose stimulated adequate antibody production to protect against infection. We hypothesized that either 0.25 or 0.5 mL IM of CDMV would stimulate antibody production comparable to the manufacturer's recommended dose. We found that the 0.25-mL dose was less effective at inducing antibodies than either the standard (1.0 mL) or 0.5-mL dose, which both yielded similar titers. The primary implication of this study informs balancing resource allocation and providing efficacious immunity. By using half the manufacturer-recommended dose, the 50% cost reduction may provide sufficient monetary incentive to implement, maintain, or modify measles vaccination programs at NHP facilities.

Figure 1.

(A) Line of fit for measles binding antibody titers, reported as the highest dilution of test serum showing antibodies against measles, with 95% CI (shaded region). A longitudinal downward trend is observed for all doses. (B) Box plots of post-vaccination antibody dilution measurements (6 and 12 mo after vaccination) suggest no difference between groups in the binding antibody titers at 6 mo after vaccination. However, animals in the quarter-dose group showed slightly lower binding antibody titer (marginally significant, P = 0.05) at 12 mo after vaccination. Red lines illustrate the medians, whiskers depict the minimal and maximal values, and the bands are the 1st and 2nd quartiles. *, P = 0.05.

Figure 2.

(A) Line of fit for neutralizing titers, reported as the highest dilution of test serum showing antibodies against measles, with 95% CI (shaded region). Similar to results from binding antibody measurement, a longitudinal downward trend is observed for all doses. (B) Box plots of post-vaccination neutralizing dilution titers (6 and 12 mo after vaccination) suggests no difference between groups in the neutralizing antibody titers at 6 mo after vaccination. However, animals in the quarter-dose group showed slightly lower albeit nonsignificant (P = 0.06) neutralizing titers at 12 mo after vaccination. Red lines illustrate the medians, whiskers depict the minimal and maximal values, and the bands are the 1st and 2nd quartiles. *, P = 0.05.