Enhanced protection against Rickettsia rickettsii infection in C3H/HeN mice by immunization with a combination of a recombinant adhesin rAdr2 and a protein fragment rOmpB-4 derived from outer membrane protein B

Gong, Wenping; Wang, Pengcheng; Xiong, Xiaolu; Jiao, Jun; Yang, Xiaomei; Wen, Bin

doi:10.1016/j.vaccine.2015.01.017

Cited by 21 publications

(28 citation statements)

References 51 publications

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“…The distinct fatality rates suggest that differences in the virulence of American and Brazilian rickettsial strains may exist; however, part of this drastic difference could also be related to other factors, such as distinct numbers of recorded cases in these two countries. Recent studies have demonstrated a vaccine-mediated protection against R. rickettsii in C3H/HeN mice, which are susceptible to infection [21][22][23][24][25]. On the other hand, R. rickettsii failed to cause disseminated disease in C3H/HePas mice [26], even though this strain is closely related to C3H/HeN.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the early treatment with doxycycline, adopted in United States (as recommended by the Centers of Disease Control [20]), but not in Brazil, may also exert an important influence in the fatality rates. In the present study, we compared the susceptibility of C3H/HeN mice, which are known to be susceptible to R. rickettsii [21][22][23][24][25], to an intravenous infection with the strains Sheila Smith (American) and Taiaçu (Brazilian) of this bacterium.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Analysis of Infection by Rickettsia rickettsii Sheila Smith and Taiaçu Strains in a Murine Model

et al. 2020

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Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease caused by Rickettsia rickettsii, which is widely distributed throughout the Americas. Over 4000 cases of RMSF are recorded annually in the United States, while only around 100 cases are reported in Brazil. Conversely, while case fatality rates in the United States oscillate around 5%, in Brazil they can surpass 70%, suggesting that differences in tick vectoring capacity, population sensitivity, and/or variability in virulence of the rickettsial strains may exist. In this study, we compared the susceptibility of C3H/HeN mice to two highly virulent strains of R. rickettsii, one from the United States (Sheila Smith) and the other from Brazil (Taiaçu). Animals inoculated with the Taiaçu strain succumbed to infection earlier and exhibited severe histological lesions in both liver and spleen sooner than mice infected with the Sheila Smith strain. These differences in survival and signs of the disease are not related to a greater proliferation of the Taiaçu strain, as there were no significant differences in the rickettsial load in mice tissues inoculated with either strain. The present study is the first step to experimentally assess differences in fatality rates of RMSF in two different regions of the American continent.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Infection by Rickettsia rickettsii Sheila Smith and Taiaçu Strains in a Murine Model

et al. 2020

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“…Class I or Class II major histocompatibility complex molecules bridge the gap between innate immunity and adaptive immunity by presenting M. tuberculosis antigens to CD4 + T cells such as 1 and 17 cells, or CD8 + T cells [164,165]. A growing number of studies have suggested that 1 and 17 cells play a central role in host protection by secreting IFN-γ, TNF-α, and IL-17 [4,[166][167][168][169][170][171][172]. However, disappointingly, some vaccines have good immune protection and safety in animal models, but unexpected safety issues still arise in clinical trials.…”

Section: Interactions Between the Host And M Tuberculosis Are Stillmentioning

confidence: 99%

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Gong

Liang

2020

BioMed Research International

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Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is one of the top ten infectious diseases worldwide, and is the leading cause of morbidity from a single infectious agent. M. tuberculosis can cause infection in several species of animals in addition to humans as the natural hosts. Although animal models of TB disease cannot completely simulate the occurrence and development of human TB, they play an important role in studying the pathogenesis, immune responses, and pathological changes as well as for vaccine research. This review summarizes the commonly employed animal models, including mouse, guinea pig, rabbit, rat, goat, cattle, and nonhuman primates, and their characteristics as used in TB vaccine research, and provides a basis for selecting appropriate animal models according to specific research needs. Furthermore, some of the newest animal models used for TB vaccine research (such as humanized animal models, zebrafish, Drosophila, and amoeba) are introduced, and their characteristics and research progress are discussed.

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“…We have demonstrated that both SFG and TG rickettsial species likely possess redundancy in the mechanisms by which this class of pathogens subverts complement-mediated killing [7]. Elucidating the various strategies evolved by pathogenic bacteria in order to evade this innate immune clearance from the blood circulation may reveal conserved proteins that could function as candidates for therapeutic intervention, which has recently been described [13, 14]. …”

Section: Discussionmentioning

confidence: 99%

“…Spotted fever group (SFG) Rickettsia sp. express a multitude of membrane-bound proteins which have been demonstrated not only to play integral roles in rickettsial pathogenesis through processes of adherence and invasion of host cells, but confer resistance to anti-bacterial host responses [6–14]. Among the characterized outer membrane proteins, Rickettsia conorii RC1281/Adr1 was demonstrated to recruit host regulatory complement protein vitronectin in order to confer resistance to serum-mediated killing [9].…”

Section: Introductionmentioning

confidence: 99%

Expression of Rickettsia Adr2 protein in E. coli is sufficient to promote resistance to complement-mediated killing, but not adherence to mammalian cells

2017

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Bacteria exposed to host serum are subject to the antibacterial effects to the complement system. However, pathogenic microorganisms have evolved mechanisms of evading this immune attack. We have previously demonstrated that at least two R. conorii antigens, RC1281/Adr1 and OmpB β-peptide, contribute to the evasion of complement-mediated killing by binding the complement regulatory proteins vitronectin and factor H. RC1282/Adr2, a protein related to Adr1, is predicted to share similar structural features, suggesting that this protein may also contribute to evasion of complement-mediated killing. Interestingly, the R. prowazekii Adr1 and Adr2(RP828) proteins were originally found to interact with host cell surface proteins, suggesting their putative roles as adhesins in this pathogenic rickettsial species. In this study, we expressed both R. conorii and R. prowazekii Adr2 on the surface of a non-adherent, serum-sensitive strain of E. coli to examine the potential role of this protein to mediate evasion of complement-mediated killing and adherence to host cells. We demonstrate that, similar to R. conorii Adr1, R. conorii and R. prowazekii Adr2 are sufficient to mediate serum resistance and to promote interaction with the host complement regulator vitronectin. Furthermore, we demonstrate that expression of Adr2 in a non-adherent strain of E. coli is insufficient to mediate adherence to cultured mammalian endothelial cells. Together, our data demonstrate that the R. conorii and R. prowazekii Adr2 protein does not participate in the interactions with mammalian cells, but rather, participates in the evasion of killing by complement.

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Enhanced protection against Rickettsia rickettsii infection in C3H/HeN mice by immunization with a combination of a recombinant adhesin rAdr2 and a protein fragment rOmpB-4 derived from outer membrane protein B

Cited by 21 publications

References 51 publications

Comparative Analysis of Infection by Rickettsia rickettsii Sheila Smith and Taiaçu Strains in a Murine Model

Comparative Analysis of Infection by Rickettsia rickettsii Sheila Smith and Taiaçu Strains in a Murine Model

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

Expression of Rickettsia Adr2 protein in E. coli is sufficient to promote resistance to complement-mediated killing, but not adherence to mammalian cells

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