Six Decades of Global Research on Bovine Babesiosis Vaccines: A Comprehensive Systematic Review and Meta-Analysis.

Abstract

Bovine babesiosis is a tick-borne disease that poses significant economic losses to global cattle production, and diverse vaccine platforms have been developed to combat it. This work critically evaluates global research on bovine babesiosis vaccines, integrating historical milestones with recent advances in antigen discovery and immunization approaches and assessing their protective efficacy through meta-analysis. Using comprehensive database searches, we identified 413 publications on bovine babesiosis vaccines, of which 168 met the inclusion criteria, spanning from 1960 to August 2025. Analysis revealed that <i>B. bovis</i> dominated the research output, followed by <i>B. bigemina</i> and <i>B. divergens</i>. Five key methodological approaches emerged: field trials, controlled experiments, immunogenicity assessments, in vitro assays, and in silico antigen analyses, with a notable shift toward immunogenicity and computational studies post-2000. Frequently studied antigens included RAP-1, MSA-2c, AMA-1, 11C5, and 12D3 (<i>B. bovis</i>); RAP-1 and GP45 (<i>B. bigemina</i>); and Bd37 (<i>B. divergens</i>). Geographically, research was concentrated in the United States, Australia, Argentina, Mexico, and France, which were identified as the top contributors in that order, primarily focusing on live and recombinant vaccines, with minimal African participation despite high cattle populations. Bibliometric analysis showed increasing publication output, with leading journals such as <i>Veterinary Parasitology</i>, <i>Infection and Immunity</i>, <i>and Parasites &amp; Vectors</i> as the top three. Thematic evolution highlighted a transition from live vaccines to recombinant and multi-epitope strategies, with increasing emphasis on conserved antigens and novel platforms. However, more field evaluations are required to determine whether these new technologies can achieve protective efficacy comparable to that of live vaccines. This work underscores the need for sustained investment, intersectoral collaboration, and validation using standardized and comparable metrics in field trials to translate laboratory innovations into effective, safe, and globally accessible vaccines against bovine babesiosis.