Exploring the landscape of Babesia bovis vaccines: progress, challenges, and opportunities

Abstract

Bovine babesiosis, caused by different Babesia spp. such as B. bovis, B. bigemina, B. divergens, and B. major, is a global disease that poses a serious threat to livestock production. Babesia bovis infections are associated with severe disease and increased mortality in adult cattle, making it the most virulent agent of bovine babesiosis. Babesia bovis parasites undergo asexual reproduction within bovine red blood cells, followed by sexual reproduction within their tick vectors, which transmit the parasite transovarially. Current control methods, including therapeutic drugs (i.e., imidocarb) have been found to lead to drug resistance. Moreover, changing environmental factors add complexity to efficient parasite control. Understanding the fundamental biology, host immune responses, and host-parasite interactions of Babesia parasites is critical for developing next-generation vaccines to control acute disease and parasite transmission. This systematic review analyzed available research papers on vaccine development and the associated immune responses to B. bovis. We compiled and consolidated the reported vaccine strategies, considering the study design and rationale of each study, to provide a systematic review of knowledge and insights for further research. Thirteen studies published since 2014 (inclusive) represented various vaccine strategies developed against B. bovis such as subunit, live attenuated, and viral vector vaccines. Such strategies incorporated B. bovis proteins or whole live parasites with the latter providing the most effective prophylaxis against bovine babesiosis. Incorporating novel research approaches, such as "omics" will enhance our understanding of parasite vulnerabilities.

Keywords: Babesia bovis; Bovine babesiosis; Immune response; Vaccine development.

Fig. 1

Life cycle of Babesia bovis. Babesia bovis has two main phases: A The sexual cycle takes place in the tick host. The sexual cycle of B. bovis is initiated when a tick ingests gametocytes of the parasite during its blood meal on a mammalian host. Following ingestion, the gametocytes differentiate into male and female gametes within the tick's gut, which fuse to form a zygote. The zygote develops into an ookinete that migrates to the tick's salivary glands as a kinete, where it may be transmitted to a new vertebrate host during tick feeding. Kinetes gain access to the hemolymph of the tick, replicate, and invade various organs. Additionally, transovarial transmission of B. bovis can also occur within the tick. Subsequently, the kinetes develop into invasive sporozoites, which are transmitted by the tick to a new vertebrate host during a blood meal. B The asexual cycle occurs in the mammalian (vertebrate) host. During the asexual cycle of B. bovis, the sporozoites invade the red blood cells (RBCs) of the bovine host and develop into trophozoites and divide by binary fission, resulting in the formation of merozoites. These merozoites continue to proliferate, developing into trophozoites and eventually give rise to new merozoites. Within the RBCs, certain merozoites undergo differentiation into male and female gametocytes, which remain within the RBCs of the bovine host. These gametocytes are then acquired by ticks during their feeding process

Fig. 2

Flow chart of the study selection and identification process. The steps were adopted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines

Fig. 3

Number of studies categorized into A publication year, B geographical region, and C type of vaccine. The 13 papers were stratified according to their publication year, geographical region, and vaccine type used in the study

Fig. 4

Scheme of immune responses in bovines infected with Babesia parasites. A Schematic of innate immunity. Innate immune responses in young calves are characterized by the swift activation of macrophages and the abundant release of interferon-γ (IFN-γ) and nitric oxide (NO). Young, naive calves have a natural resistance to Babesia infection and typically survive exposure to Babesia-infected ticks in endemic areas. In contrast, adult animals are more susceptible to Babesia infection, which often results in acute and fatal babesiosis. However, if animals survive the acute infection, they may develop chronic babesiosis and produce life-long protective immune responses. Additionally, the innate immune response is more pronounced in young animals compared to adult animals. B Schematic of adaptive immunity in persistently infected or vaccinated animals with live attenuated vaccine. Macrophages and protective neutralizing antibodies are deemed critical for controlling parasitemia in these animals