Abstract
To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.
Highlights
The World Health Organization (WHO), the World Organization for Animal Health (OIE), the Food and Agricultural Organization of the United Nations (FAO), and the Global Alliance for Rabies Control (GARC) have endorsed a plan to eliminate human deaths from dog-mediated rabies by 2030 [1]
For the immunogenicity data analysis, we report the geometric mean concentration (GMC) of rabies virus neutralizing antibodies (RVNA) titers and the proportion of subjects seroresponding for the treatment group, 21 days after first rabies vaccine (RV) injection at 6 weeks
We show that puppies born to dams vaccinated against rabies do not have appreciable levels of maternally-derived antibodies at 6 weeks of age, and that the rabies vaccine is immunogenic when administered to puppies at this age
Summary
The World Health Organization (WHO), the World Organization for Animal Health (OIE), the Food and Agricultural Organization of the United Nations (FAO), and the Global Alliance for Rabies Control (GARC) have endorsed a plan to eliminate human deaths from dog-mediated rabies by 2030 [1]. Rabies vaccines recommended by the WHO and the OIE for the control of rabies in dogs in endemic areas are injectable inactivated cell-culture vaccines [4,5]. Primary vaccination with these vaccines is recommended by manufacturers as a single dose at 12–14 weeks of age, followed by a repeat dose one year later and subsequent revaccination every three years. In the context of mass dog rabies vaccination campaigns, international and national guidelines allow for adaptation of vaccination schedules from those recommended by vaccine manufacturers, including vaccination of dogs younger than 12 weeks without regard for maternal immune status [4,5,6]. Evaluation of the effect of maternal immune status on the immunogenicity of the vaccine in this age group is important in the context of increased dog vaccination in the Zero by 30 strategic plan, as more puppies will be born to vaccinated dams (mothers)
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