Facing the challenges of multidrug-resistant Acinetobacter baumannii: progress and prospects in the vaccine development

Figures & data

Table 1. List of developed A. baumannii vaccine evaluated in animal models

Type of Vaccine	Virulence/Potential Target	Route of administration	Vaccination mode	Ref
Formalin-inactivated	Whole cells	Active: Intramuscular; Passive: Intravenous	Active and passive	^Citation47
	Antibiotic-exposed whole cells	Intramuscular	Active	^Citation49
	LPS-deficient IWC	Intramuscular	Active	^Citation56
Bacterial Ghosts	LPS/surface	Oral, subcutaneous, intramuscular, intraperitoneal	Active	^Citation50
Cells component	Outer membrane complexes (OMCs)	Active: Intramuscular; Passive: Intravenous	Active and passive	^Citation52
	LPS-free OMCs	Intramuscular	Active	^Citation55
	Outer membrane vesicles (OMVs)	Active: Intramuscular; Passive: Intravenous	Active and passive	^Citation53
	LPS-free OMVs	Intramuscular	Active	^Citation57
Bacterial polysaccharides	Poly-N-acetyl-β-(1,6)-glucosamine (PNAG)	Anti-sera production: Subcutaneous+Intravenous; Immunization: Intranasal	Passive	^Citation48
	K1 capsular polysaccharide (CPS)	Antisera production: Intraperitoneal; Immunization: Subcutaneous	Passive	^Citation62
Subunit vaccine/recombinant vaccine	OmpA	Active: Subcutaneous; Passive: Intraperitoneal	Active and passive	^Citation68
	OmpA	Intranasal	Active	^Citation69
	Trimeric autotransporter protein (Ata)	Antisera production: Subcutaneous; Immunization: Intravenous	Active and passive	^Citation76
	Omp22	Active: Subcutaneous; Passive: Intravenous	Active and passive	^Citation73
	BamA	Active: Intraperitoneal; Passive: Intravenous	Active and passive	^Citation74
	FilF	Subcutaneous	Active	^Citation82
	OmpK	Intramuscular	Active	^Citation86
	FK1B	Intramuscular	Active	^Citation86
	OmpP1	Intramuscular	Active	^Citation86
	Hybrid ZnuD protein	Active: Subcutaneous; Passive: Intravenous	Active and passive	^Citation80
	Blp1	Active: Intramuscular; Passive: Intraperitoneal	Active and passive	^Citation32
	smpA and/or PLD	Active: Subcutaneous; Passive: Intravenous	Active and passive	^Citation78
DNA vaccine	OmpA	Intramuscular	Active	^Citation70
	OmpA and Pal	Intramuscular	Active	^Citation71

McConnell MJ, Pachon J. Active and passive immunization against Acinetobacter baumannii using an inactivated whole cell vaccine. Vaccine. 2010;29:1–5. 1873-2518 (Electronic). doi:10.1016/j.vaccine.2010.10.052.

 PubMed Web of Science ®Google Scholar

Shu MH, MatRahim N, NorAmdan N, Pang SP, Hashim SH, Phoon WH, AbuBakar S. An inactivated antibiotic-exposed whole-cell vaccine enhances bactericidal activities against multidrug-resistant Acinetobacter baumannii. Sci Rep. 2016;6:22332. 2045-2322 (Electronic). doi:10.1038/srep22332.

 PubMed Web of Science ®Google Scholar

Garcia-Quintanilla M, Pulido MR, Pachon J, McConnell MJ. Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection. PLoS One. 2014;9(12):e114410. doi:10.1371/journal.pone.0114410.

 PubMed Web of Science ®Google Scholar

Sheweita SA, Batah AM, Ghazy AA, Hussein A, Amara AA. A new strain of Acinetobacter baumannii and characterization of its ghost as a candidate vaccine. J Infect Public Health. 2019;12(6):831–42. doi:10.1016/j.jiph.2019.05.009.

 PubMed Web of Science ®Google Scholar

McConnell MJ, Dominguez-Herrera J, Smani Y, Lopez-Rojas R, Docobo-Perez F, Pachon J. Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii. Infect Immun. 2011;79(1):518–26. doi:10.1128/IAI.00741-10.

 PubMed Web of Science ®Google Scholar

Pulido MR, Garcia-Quintanilla M, Pachon J, McConnell MJ. Immunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection. Vaccine. 2018;36(29):4153–56. doi:10.1016/j.vaccine.2018.05.113.

 PubMed Web of Science ®Google Scholar

McConnell MJ, Rumbo C, Bou G, Pachón J. Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii. Vaccine. 2011;29:5705–10.

 PubMed Web of Science ®Google Scholar

Pulido MR, Garcia-Quintanilla M, Pachon J, McConnell MJ. A lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection. Vaccine. 2020;38(4):719–24. doi:10.1016/j.vaccine.2019.11.043.

 PubMed Web of Science ®Google Scholar

Bentancor LV, O’Malley JM, Bozkurt-Guzel C, Gb P, Maira-Litrán T. Poly-n-acetyl-beta-(1-6)-glucosamine is a target for protective immunity against Acinetobacter baumannii infections. Infect Immun. 2012;80:651–56. 1098-5522 (Electronic). doi:10.1128/IAI.05653-11.

 PubMed Web of Science ®Google Scholar

Russo TA, Beanan JM, Olson R, MacDonald U, Cox AD, Michael FS, Vinogradov EV, Spellberg B, Luke-Marshall NR, Campagnari AA. The k1 capsular polysaccharide from Acinetobacter baumannii is a potential therapeutic target via passive immunization. Infect Immun. 2013;81:915–22. 1098-5522 (Electronic). doi:10.1128/IAI.01184-12.

 PubMed Web of Science ®Google Scholar

Luo G, Lin L, Ibrahim AS, Baquir B, Pantapalangkoor P, Bonomo RA, Doi Y, Adams MD, Russo TA, Spellberg B. Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection. PLoS One. 2012;7:e29446.

 PubMed Web of Science ®Google Scholar

Zhang X, Yang T, Cao J, Sun J, Dai W, Zhang L. Mucosal immunization with purified OmpA elicited protective immunity against infections caused by multidrug-resistant Acinetobacter baumannii. Microb Pathog. 2016;96:20–25. 1096-1208 (Electronic). doi:10.1016/j.micpath.2016.04.019.

 PubMed Web of Science ®Google Scholar

Bentancor LV, Routray A, Bozkurt-Guzel C, Camacho-Peiro A, Pier GB, Maira-Litrán T. Evaluation of the trimeric autotransporter ata as a vaccine candidate against Acinetobacter baumannii infections. Infect Immun. 2012;80:3381–88. 1098-5522 (Electronic). doi:10.1128/IAI.06096-11.

 PubMed Web of Science ®Google Scholar

Huang W, Yao Y, Wang S, Xia Y, Yang X, Long Q, Sun W, Liu C, Li Y, Chu X, et al. Immunization with a 22-kda outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii. Sci Rep. 2016;6:20724. 2045-2322 (Electronic). doi:10.1038/srep20724.

 PubMed Web of Science ®Google Scholar

Singh R, Capalash N, Sharma P. Immunoprotective potential of bama, the outer membrane protein assembly factor, against MDR Acinetobacter baumannii. Sci Rep. 2017;7(1):12411. doi:10.1038/s41598-017-12789-3.

 PubMed Web of Science ®Google Scholar

Singh R, Garg N, Shukla G, Capalash N, Sharma P. Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, filf, predicted in silico as a potential vaccine candidate. Front Microbiol. 2016;7. 1664-302X (Print). doi:10.3389/fmicb.2016.00158.

 Web of Science ®Google Scholar

Chiang MH, Sung WC, Lien SP, Chen YZ, Lo AFY, Huang JH, Kuo SC, Chong P. Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology. Hum Vaccin Immunother. 2015;11:1065–73. 2164-554X (Electronic). doi:10.1080/21645515.2015.1010910.

 PubMed Web of Science ®Google Scholar

Qamsari MM, Rasooli I, Chaudhuri S, Astaneh SDA, Schryvers AB. Hybrid antigens expressing surface loops of znud from Acinetobacter baumannii is capable of inducing protection against infection. Front Immunol. 2020;11:158–158. doi:10.3389/fimmu.2020.00158.

 PubMed Web of Science ®Google Scholar

Skerniskyte J, Karazijaite E, Deschamps J, Krasauskas R, Armalyte J, Briandet R, Suziedeliene E. Blp1 protein shows virulence-associated features and elicits protective immunity to Acinetobacter baumannii infection. BMC Microbiol. 2019;19(1):259. doi:10.1186/s12866-019-1615-3.

 PubMed Web of Science ®Google Scholar

Li H, Tan H, Hu Y, Pan P, Su X, Hu C. Small protein a and phospholipase d immunization serves a protective role in a mouse pneumonia model of Acinetobacter baumannii infection. Mol Med Rep. 2017;16(2):1071–78. doi:10.3892/mmr.2017.6688.

 PubMed Web of Science ®Google Scholar

Ansari H, Tahmasebi-Birgani M, Bijanzadeh M, Doosti A, Kargar M. Study of the immunogenicity of outer membrane protein a (OmpA) gene from Acinetobacter baumannii as DNA vaccine candidate in vivo. Iran J Basic Med Sci. 2019;22(6):669–75. doi:10.22038/ijbms.2019.30799.7427.

 PubMed Web of Science ®Google Scholar

Lei L, Yang F, Zou J, Jing H, Zhang J, Xu W, Zou Q, Zhang J, Wang X. DNA vaccine encoding ompa and pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection. Mol Biol Rep. 2019;46(5):5397–408. doi:10.1007/s11033-019-04994-2.

 PubMed Web of Science ®Google Scholar