Safety and Transcriptome Analysis of Live Attenuated Brucella Vaccine Strain S2 on Non-pregnant Cynomolgus Monkeys Without Abortive Effect on Pregnant Cynomolgus Monkeys

Abstract

Brucellosis, caused by Brucella spp., is an important zoonotic disease leading to enormous economic losses in livestock, posing a great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2, a safe and effective vaccine, is widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly humans. In this study, we used cynomolgus monkey as an animal model to evaluate the safety of the S2 vaccine strain on primates. In addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe for cynomolgus monkeys. The transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly upregulated and 315 were remarkably downregulated. The Gene Ontology (GO) classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were involved in various biological processes (BPs), including the chemokine signaling pathway, actin cytoskeleton regulation, the defense response, immune system processing, and the type-I interferon signaling pathway. The molecular functions of the DEGs were mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding, and actin-binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex, and blood microparticle. Our findings alleviate the concerns over the safety of the S2 vaccine on primates and provide a genetic basis for the response from a mammalian host following vaccination with the S2 vaccine.

The Role of Intestinal Microbial Metabolites in the Immunity of Equine Animals Infected With Horse Botflies

“…The GO functional enrichment analysis indicated that the most significantly different GO term was signaling pattern recognition receptor activity, while the defense response function contained the largest number of unigenes (64) (Supplementary Figure S6). This result is consistent with the findings of another study, where the defense response function is abundant in monkeys after immunization (79).…”

In silico designed novel multi-epitope mRNA vaccines against Brucella by targeting extracellular protein BtuB and LptD

“…The primary attenuated live vaccines for brucellosis in China include Brucella melitensis strain M5, Brucella suis strain S2, and Brucella abortus strain A19 27 . However, there are many shortcomings, such as persistent infection in vaccinated animals, risk of toxicity reversal, lack of lasting protection, interference with brucellosis diagnosis and so on 28 .Developing a new vaccine needs to verify its effectiveness and safety, which is a time-consuming and expensive process.…”

The advances of the Chinese Brucella suis strain 2 vaccine

“…However, no safe and effective vaccine has been developed and licensed for human brucellosis so far. China has licensed B. melitensis strain M5, B. suis strain S2, and B. abortus strain A19 as its nationwide approved animal brucellosis vaccines [18], and among them, the S2 vaccine was approved as a multivalent vaccine against the three Brucella species in cattle, small ruminants, and swine, respectively [18,19]. Here, we will discuss the development of the S2 vaccine in China, biological properties of the S2 vaccine as well as its wide use in vaccination programs of China in pursuit of standardization and validation of a harmonized national vaccination campaign in cattle, small ruminants, and swine.…”