Sex-differential non-specific effects of adjuvanted and non-adjuvanted rabies vaccines versus placebo on all-cause mortality in dogs (NERVE-Dog study): a study protocol for a randomized controlled trial with a nested case-control study.

Autor: Knobel DL; Department of Biomedical Sciences, Ross University School of Veterinary Medicine, Basseterre, St Kitts and Nevis. dknobel@rossvet.edu.kn.; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. dknobel@rossvet.edu.kn., Conan A; Center for Applied One Health Research and Policy Advice, City University of Hong Kong, Kowloon, Hong Kong, Special Administrative Region of China., Toka FN; Department of Biomedical Sciences, Ross University School of Veterinary Medicine, Basseterre, St Kitts and Nevis., Arega SM; Department of Public and Community Health, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya., Byaruhanga C; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa.; Department of Public and Community Health, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya., Ogola E; Department of Public and Community Health, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya., Muok EMO; Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya., Crafford JE; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa., Leisewitz AL; Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa.; Present Address: Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, USA., Quan M; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa., Thrall MA; Department of Biomedical Sciences, Ross University School of Veterinary Medicine, Basseterre, St Kitts and Nevis.
Jazyk: angličtina
Zdroj: BMC veterinary research [BMC Vet Res] 2022 Oct 01; Vol. 18 (1), pp. 363. Date of Electronic Publication: 2022 Oct 01.
DOI: 10.1186/s12917-022-03455-6
Abstrakt: Background: It has been proposed that childhood vaccines in high-mortality populations may have substantial impacts on mortality rates that are not explained by the prevention of targeted diseases, nor conversely by typical expected adverse reactions to the vaccines, and that these non-specific effects (NSEs) are generally more pronounced in females. The existence of these effects, and any implications for the development of vaccines and the design of vaccination programs to enhance safety, remain controversial. One area of controversy is the reported association of non-live vaccines with increased female mortality. In a previous randomized controlled trial (RCT), we observed that non-live alum-adjuvanted animal rabies vaccine (ARV) was associated with increased female but not male mortality in young, free-roaming dogs. Conversely, non-live non-adjuvanted human rabies vaccine (NRV) has been associated with beneficial non-specific effects in children. Alum adjuvant has been shown to suppress Th1 responses to pathogens, leading us to hypothesize that alum-adjuvanted rabies vaccine in young dogs has a detrimental effect on female survival by modulating the immune response to infectious and/or parasitic diseases. In this paper, we present the protocol of a 3-arm RCT comparing the effect of alum-adjuvanted rabies vaccine, non-adjuvanted rabies vaccine and placebo on all-cause mortality in an owned, free-roaming dog population, with causal mediation analysis of the RCT and a nested case-control study to test this hypothesis.
Methods: Randomised controlled trial with a nested case-control study.
Discussion: We expect that, among the placebo group, males will have higher mortality caused by higher pathogen loads and more severe disease, as determined by haematological parameters and inflammatory biomarkers. Among females, we expect that there will be no difference in mortality between the NRV and placebo groups, but that the ARV group will have higher mortality, again mediated by higher pathogen loads and more severe disease. We anticipate that these changes are preceded by shifts in key serum cytokine concentrations towards an anti-inflammatory immune response in females. If confirmed, these results will provide a rational basis for mitigation of detrimental NSEs of non-live vaccines in high-mortality populations.
(© 2022. The Author(s).)
Databáze: MEDLINE
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