Estrutura Tridimensional da Major Surface Protease de Leishmania guyanensis Resolvida por Modelagem Comparativa

Abstract Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

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Lipoproteins Are Responsible for the Pro-Inflammatory Property of Staphylococcus aureus Extracellular Vesicles

International Journal of Molecular Sciences ◽

10.3390/ijms22137099 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7099

Author(s):

Pradeep Kumar Kopparapu ◽

Meghshree Deshmukh ◽

Zhicheng Hu ◽

Majd Mohammad ◽

Marco Maugeri ◽

...

Keyword(s):

Extracellular Vesicles ◽

Inflammatory Responses ◽

Surface Proteins ◽

Host Cells ◽

Immune Stimulation ◽

Domains Of Life ◽

Major Surface ◽

Staphylococcal Aureus

Staphylococcal aureus (S. aureus), a Gram-positive bacteria, is known to cause various infections. Extracellular vesicles (EVs) are a heterogeneous array of membranous structures secreted by cells from all three domains of life, i.e., eukaryotes, bacteria, and archaea. Bacterial EVs are implied to be involved in both bacteria–bacteria and bacteria–host interactions during infections. It is still unclear how S. aureus EVs interact with host cells and induce inflammatory responses. In this study, EVs were isolated from S. aureus and mutant strains deficient in either prelipoprotein lipidation (Δlgt) or major surface proteins (ΔsrtAB). Their immunostimulatory capacities were assessed both in vitro and in vivo. We found that S. aureus EVs induced pro-inflammatory responses both in vitro and in vivo. However, this activity was dependent on lipidated lipoproteins (Lpp), since EVs isolated from the Δlgt showed no stimulation. On the other hand, EVs isolated from the ΔsrtAB mutant showed full immune stimulation, indicating the cell wall anchoring of surface proteins did not play a role in immune stimulation. The immune stimulation of S. aureus EVs was mediated mainly by monocytes/macrophages and was TLR2 dependent. In this study, we demonstrated that not only free Lpp but also EV-imbedded Lpp had high pro-inflammatory activity.

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An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

npj Vaccines ◽

10.1038/s41541-020-00274-4 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Lucie Jelínková ◽

Hugo Jhun ◽

Allison Eaton ◽

Nikolai Petrovsky ◽

Fidel Zavala ◽

...

Keyword(s):

Mouse Model ◽

Malaria Vaccine ◽

High Titer ◽

Circumsporozoite Protein ◽

Infection Model ◽

Vaccine Platform ◽

Junctional Region ◽

Mouse Infection Model ◽

Virus Like Particle ◽

Major Surface

AbstractA malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.

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Helium in diamonds unravels over a billion years of craton metasomatism

Nature Communications ◽

10.1038/s41467-021-22860-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yaakov Weiss ◽

Yael Kiro ◽

Cornelia Class ◽

Gisela Winckler ◽

Jeff W. Harris ◽

...

Keyword(s):

Continental Lithosphere ◽

Late Mesozoic ◽

Tectonic Events ◽

Upper Limit ◽

Age Limits ◽

Fluid Bearing ◽

Major Surface ◽

Chemical Events

AbstractChemical events involving deep carbon- and water-rich fluids impact the continental lithosphere over its history. Diamonds are a by-product of such episodic fluid infiltrations, and entrapment of these fluids as microinclusions in lithospheric diamonds provide unique opportunities to investigate their nature. However, until now, direct constraints on the timing of such events have not been available. Here we report three alteration events in the southwest Kaapvaal lithosphere using U-Th-He geochronology of fluid-bearing diamonds, and constrain the upper limit of He diffusivity (to D ≈ 1.8 × 10−19 cm2 s−1), thus providing a means to directly place both upper and lower age limits on these alteration episodes. The youngest, during the Cretaceous, involved highly saline fluids, indicating a relationship with late-Mesozoic kimberlite eruptions. Remnants of two preceding events, by a Paleozoic silicic fluid and a Proterozoic carbonatitic fluid, are also encapsulated in Kaapvaal diamonds and are likely coeval with major surface tectonic events (e.g. the Damara and Namaqua–Natal orogenies).

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Immune response of calves inoculated with proteins ofAnaplasma marginale bound to an immunostimulant complex

Revista Brasileira de Parasitologia Veterinária ◽

10.1590/s1984-29612013000200044 ◽

2013 ◽

Vol 22 (2) ◽

pp. 253-259 ◽

Cited By ~ 1

Author(s):

Marcela Ribeiro Gasparini ◽

Rafael Felipe da Costa Vieira ◽

Denise Amaral Gomes do Nascimento ◽

João Luis Garcia ◽

Odilon Vidotto ◽

...

Keyword(s):

Immune Response ◽

Current Knowledge ◽

Surface Proteins ◽

Control Group ◽

Humoral Immune ◽

The Third ◽

Additional Testing ◽

Major Surface Proteins ◽

Cattle Herds ◽

Major Surface

Despite our current knowledge of the immunology, pathology, and genetics of Anaplasma marginale, prevention in cattle is currently based on old standbys, including live attenuated vaccines, antibiotic treatment, and maintaining enzootic stability in cattle herds. In the present study, we evaluated the use of an immunostimulant complex (ISCOMATRIX) adjuvant, associated with a pool of recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5) to improve the humoral immune response triggered in calves mainly by IgG2. Ten calves were divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1); 2 calves were inoculated with ISCOMATRIX adjuvant (G2); and 4 calves received saline (G3). Three inoculations were administered at 21-day intervals. In G1, the calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days after the second inoculation, compared to the control group (p < 0.05), and G1 calves remained above the cut-off value 28 days after the third inoculation (p < 0.05). The post-immunized sera from calves in G1 reacted specifically for each of the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific seroconversion in calves. Therefore, additional testing to explore the protection induced by rMSPs, both alone and in conjunction with proteins previously identified as subdominant epitopes, is warranted.

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Three strains of Wolbachia pipientis and high rates of infection in Iranian sandfly species

Bulletin of Entomological Research ◽

10.1017/s0007485313000631 ◽

2014 ◽

Vol 104 (2) ◽

pp. 195-202 ◽

Cited By ~ 4

Author(s):

A. Bordbar ◽

S. Soleimani ◽

F. Fardid ◽

M.R. Zolfaghari ◽

P. Parvizi

Keyword(s):

Protein Gene ◽

Surface Protein ◽

Male And Female ◽

Wolbachia Pipientis ◽

Major Surface Protein ◽

Zoonotic Cutaneous Leishmaniasis ◽

Geographical Regions ◽

Surface Protein Gene ◽

Major Surface ◽

Zoonotic Visceral Leishmaniasis

AbstractIndividual wild-caught sandflies from Iran were examined for infections of Wolbachia pipientis by targeting the major surface protein gene wsp of this intracellular α-proteobacterium. In total, 638 male and female sandflies were screened, of which 241 were found to be positive for one of three wsp haplotypes. Regardless of geographical origins and habitats, Phlebotomus (Phlebotomus) papatasi and other sandfly species were found to be infected with one common, widespread strain of A-group W. pipientis (Turk 54, GenBank accession EU780683; AY288297). In addition, a new A-group haplotype (Turk07, GenBank accession KC576916) was isolated from Phlebotomus (Paraphlebotomus) mongolensis and Phlebotomus (Pa.) caucasicus, and a new B-group haplotype (AZ2331, GenBank accession JX488735) was isolated from Phlebotomus (Larroussius) perfiliewi. Therefore, Wolbachia was found to occur in at least three of the incriminated vectors of zoonotic cutaneous leishmaniasis and zoonotic visceral leishmaniasis in different geographical regions of Iran. It may provide a new tool for the future control of leishmaniasis.

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The M Protein Is Dispensable for Maturation of Streptococcal Cysteine Protease SpeB

Infection and Immunity ◽

10.1128/iai.73.2.859-864.2005 ◽

2005 ◽

Vol 73 (2) ◽

pp. 859-864 ◽

Cited By ~ 9

Author(s):

Björn Zimmerlein ◽

Hae-Sun Park ◽

Shaoying Li ◽

Andreas Podbielski ◽

P. Patrick Cleary

Keyword(s):

Cysteine Protease ◽

Protease Activity ◽

Active Form ◽

Surface Protein ◽

M Protein ◽

Cysteine Protease Activity ◽

Group A ◽

Streptococcal Pyrogenic Exotoxin B ◽

Major Surface ◽

Culture Supernatants

ABSTRACT The streptococcal pyrogenic exotoxin B (SpeB) is an important virulence factor of group A streptococci (GAS) with cysteine protease activity. Maturation of SpeB to a proteolytically active form was suggested to be dependent on cell-wall-anchored M1 protein, the major surface protein of GAS (M. Collin and A. Olsén, Mol. Microbiol. 36:1306-1318, 2000). Collin and Olsén showed that mutant GAS strains expressing truncated M protein secrete a conformationally different form of unprocessed SpeB with no proteolytic activity. Alternatively, we hypothesized that a truncated M protein may interfere with processing of this secreted protease, and therefore we tested cysteine protease activity in genetically defined mutant strains that express either no M protein or membrane-anchored M protein with an in-frame deletion of the AB repeat region. Measurements of SpeB activity by cleavage of a substrate n-benzoyl-Pro-Phe-Arg-p-nitroanilide hydrochloride showed that the proteolytic activities in culture supernatants of both mutants were similar to those from the wild-type strain. In addition, Western blot analysis of culture supernatants showed that SpeB expression and processing to a mature form was unaffected by either deletion mutation. Therefore, we conclude that M protein is not required for maturation of the streptococcal cysteine protease SpeB.

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