PMID- 34992597 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20221221 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Epitope-Based Vaccine of a Brucella abortus Putative Small RNA Target Induces Protection and Less Tissue Damage in Mice. PG - 778475 LID - 10.3389/fimmu.2021.778475 [doi] LID - 778475 AB - Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and animals. Currently available live attenuated vaccines against brucellosis still have drawbacks. Therefore, subunit vaccines, produced using epitope-based antigens, have the advantage of being safe, cost-effective and efficacious. Here, we identified B. abortus small RNAs expressed during early infection with bone marrow-derived macrophages (BMDMs) and an apolipoprotein N-acyltransferase (Int) was identified as the putative target of the greatest expressed small RNA. Decreased expression of Int was observed during BMDM infection and the protein sequence was evaluated to rationally select a putative immunogenic epitope by immunoinformatic, which was explored as a vaccinal candidate. C57BL/6 mice were immunized and challenged with B. abortus, showing lower recovery in the number of viable bacteria in the liver, spleen, and axillary lymph node and greater production of IgG and fractions when compared to non-vaccinated mice. The vaccinated and infected mice showed the increased expression of TNF-alpha, IFN-gamma, and IL-6 following expression of the anti-inflammatory genes IL-10 and TGF-beta in the liver, justifying the reduction in the number and size of the observed granulomas. BMDMs stimulated with splenocyte supernatants from vaccinated and infected mice increase the CD86+ marker, as well as expressing greater amounts of iNOS and the consequent increase in NO production, suggesting an increase in the phagocytic and microbicidal capacity of these cells to eliminate the bacteria. CI - Copyright (c) 2021 Oliveira, Brancaglion, Santos, Araujo, Novaes, Santos, Oliveira, Corsetti and de Almeida. FAU - Oliveira, Karen Cristina AU - Oliveira KC AD - Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas, Brazil. FAU - Brancaglion, Gustavo Andrade AU - Brancaglion GA AD - Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas, Brazil. FAU - Santos, Natalia C M AU - Santos NCM AD - Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas, Brazil. FAU - Araujo, Leonardo P AU - Araujo LP AD - Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas, Brazil. FAU - Novaes, Evandro AU - Novaes E AD - Department of Biology, Federal University of Lavras, Lavras, Brazil. FAU - Santos, Renato de Lima AU - Santos RL AD - Department of Clinic and Veterinary Surgery, Veterinary School, Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Oliveira, Sergio Costa AU - Oliveira SC AD - Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Corsetti, Patricia Paiva AU - Corsetti PP AD - Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas, Brazil. FAU - de Almeida, Leonardo Augusto AU - de Almeida LA AD - Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas, Brazil. LA - eng GR - R01 AI116453/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211221 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antigens, Bacterial) RN - 0 (Brucella Vaccine) RN - 0 (RNA, Bacterial) RN - 0 (Vaccines, Subunit) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.- (apolipoprotein N-acyltransferase) SB - IM MH - Acyltransferases/genetics MH - Animals MH - Antigens, Bacterial/genetics/immunology MH - Bacterial Zoonoses/immunology/microbiology/*prevention & control MH - Brucella Vaccine/administration & dosage/genetics/*immunology MH - Brucella abortus/genetics/*immunology MH - Brucellosis/immunology/microbiology/*prevention & control MH - Computer Simulation MH - Disease Models, Animal MH - Epitope Mapping/methods MH - Humans MH - Immunogenicity, Vaccine MH - Macrophages/immunology/microbiology MH - Mice MH - Primary Cell Culture MH - RNA, Bacterial/genetics/isolation & purification MH - Vaccines, Subunit/administration & dosage/immunology PMC - PMC8724193 OTO - NOTNLM OT - Brucella abortus OT - apolipoprotein N-acyltransferase OT - brucellosis OT - immune response OT - reverse vaccinology OT - vaccine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/08 06:00 MHDA- 2022/02/15 06:00 PMCR- 2021/01/01 CRDT- 2022/01/07 06:23 PHST- 2021/09/16 00:00 [received] PHST- 2021/12/03 00:00 [accepted] PHST- 2022/01/07 06:23 [entrez] PHST- 2022/01/08 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.778475 [doi] PST - epublish SO - Front Immunol. 2021 Dec 21;12:778475. doi: 10.3389/fimmu.2021.778475. eCollection 2021.