scholarly journals A dose-response study in mice of a tetravalent recombinant dengue envelope domain III protein secreted from insect cells

2020 ◽  
Author(s):  
Lijun Shao ◽  
Zheng Pang ◽  
Yu Bi ◽  
Zhenhua Li ◽  
Weiping Lin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Humoral Immunity ◽  
Insect Cells ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Potential Vaccine ◽  
Domain Iii ◽  
Dose Response Study ◽  
Development Methods ◽  
Medium Dose

Abstract Background: DENV is the most globally prevalent mosquito-transmitted virus. Induction of a broadly and potently immune response is desirable for dengue vaccine development. Methods: We constructed a secreted tetravalent EDⅢ protein from eukaryotic cells and established a MAC-ELISA method for DENV diagnosis. This work aimed to evaluate the immune responses in mice of several formulations of rEDIII containing different amounts of the tetravalent protein. Results: We demonstrated that the tetravalent protein induced humoral immunity against all four serotypes of DENV, even at the lowest dose assayed. Besides, cellular immunities against DENV-1 and DENV-2 were elicited by medium dose group. Importantly, the immune responses induced by the tetravalent formulation were functional in clearing DENV-2 in circulation of mice. Conclusions: We believe that the tetravalent formulation of secreted EDⅢ protein is a potential vaccine candidate against DENV and suggest further detailed studies of this formulation in nonhuman primates. Keywords: Dengue virus; Tetravalent; Humoral immunity; Cellular immunity; Vaccine

A dose-response study in mice of a tetravalent vaccine candidate composed of domain III-capsid proteins from dengue viruses

2017 ◽  
Vol 162 (8) ◽  
pp. 2247-2256 ◽  
Author(s):  
Iris Valdés ◽  
Ernesto Marcos ◽  
Edith Suzarte ◽  
Yusleidi Pérez ◽  
Enma Brown ◽  
...  
Keyword(s):  
Dose Response ◽  
Vaccine Candidate ◽  
Capsid Proteins ◽  
Dengue Viruses ◽  
Tetravalent Vaccine ◽  
Domain Iii ◽  
Dose Response Study

scholarly journals Identification of lipid A deacylase as a novel, highly conserved and protective antigen against enterohemorrhagic Escherichia coli

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maricarmen Rojas-Lopez ◽  
Manuele Martinelli ◽  
Valentina Brandi ◽  
Grégory Jubelin ◽  
Fabio Polticelli ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Vaccine Candidate ◽  
Bacterial Load ◽  
Enterohemorrhagic Escherichia Coli ◽  
Protein Antigens ◽  
E Coli ◽  
Epidemiology Data ◽  
Potential Vaccine

AbstractEnterohemorrhagic E. coli (EHEC) is a major cause of large outbreaks worldwide associated with hemorrhagic colitis and hemolytic uremic syndrome. While vaccine development is warranted, a licensed vaccine, specific for human use, against EHEC is not yet available. In this study, the reverse vaccinology approach combined with genomic, transcriptional and molecular epidemiology data was applied on the EHEC O157:H7 genome to select new potential vaccine candidates. Twenty-four potential protein antigens were identified and one of them (MC001) was successfully expressed onto Generalized Modules for Membrane Antigens (GMMA) delivery system. GMMA expressing this vaccine candidate was immunogenic, raising a specific antibody response. Immunization with the MC001 candidate was able to reduce the bacterial load of EHEC O157:H7 strain in feces, colon and caecum tissues after murine infection. MC001 is homologue to lipid A deacylase enzyme (LpxR), and to our knowledge, this is the first study describing it as a potential vaccine candidate. Gene distribution and sequence variability analysis showed that MC001 is present and conserved in EHEC and in enteropathogenic E. coli (EPEC) strains. Given the high genetic variability among and within E. coli pathotypes, the identification of such conserved antigen suggests that its inclusion in a vaccine might represent a solution against major intestinal pathogenic strains.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

scholarly journals Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 307 ◽  
Author(s):  
César López-Camacho ◽  
Giuditta De Lorenzo ◽  
Jose Luis Slon-Campos ◽  
Stuart Dowall ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Protein Domain ◽  
Virus Envelope ◽  
Zikv Infection ◽  
Domain Iii ◽  
Open Question

The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.

scholarly journals A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 850
Author(s):  
Surapong Koonpaew ◽  
Challika Kaewborisuth ◽  
Kanjana Srisutthisamphan ◽  
Asawin Wanitchang ◽  
Theeradej Thaweerattanasinp ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Mdck Cells ◽  
Chimeric Gene ◽  
Cell Mediated Immunity ◽  
Single Cycle ◽  
Virus Envelope

The use of virus-vectored platforms has increasingly gained attention in vaccine development as a means for delivering antigenic genes of interest into target hosts. Here, we describe a single-cycle influenza virus-based SARS-CoV-2 vaccine designated as scPR8-RBD-M2. The vaccine utilizes the chimeric gene encoding 2A peptide-based bicistronic protein cassette of the SARS-CoV-2 receptor-binding domain (RBD) and influenza matrix 2 (M2) protein. The C-terminus of the RBD was designed to link with the cytoplasmic domain of the influenza virus hemagglutinin (HA) to anchor the RBD on the surface of producing cells and virus envelope. The chimeric RBD-M2 gene was incorporated in place of the HA open-reading frame (ORF) between the 3′ and 5′ UTR of HA gene for the virus rescue in MDCK cells stably expressing HA. The virus was also constructed with the disrupted M2 ORF in segment seven to ensure that M2 from the RBD-M2 was utilized. The chimeric gene was intact and strongly expressed in infected cells upon several passages, suggesting that the antigen was stably maintained in the vaccine candidate. Mice inoculated with scPR8-RBD-M2 via two alternative prime-boost regimens (intranasal-intranasal or intranasal-intramuscular routes) elicited robust mucosal and systemic humoral immune responses and cell-mediated immunity. Notably, we demonstrated that immunized mouse sera exhibited neutralizing activity against pseudotyped viruses bearing SARS-CoV-2 spikes from various variants, albeit with varying potency. Our study warrants further development of a replication-deficient influenza virus as a promising SARS-CoV-2 vaccine candidate.

scholarly journals Evaluation of Recombinant Lipidated P2086 Protein as a Vaccine Candidate for Group B Neisseria meningitidis in a Murine Nasal Challenge Model

2005 ◽  
Vol 73 (10) ◽  
pp. 6838-6845 ◽  
Author(s):  
Duzhang Zhu ◽  
Ying Zhang ◽  
Vicki Barniak ◽  
Liesel Bernfield ◽  
Alan Howell ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Active Immunization ◽  
Human Beings ◽  
Nasal Tissue ◽  
Potential Vaccine ◽  
Group B ◽  
Different Strains

ABSTRACT Neisseria meningitidis is a major causative agent of bacterial meningitis in human beings, especially among young children (≤2 years of age). Prevention of group B meningococcal disease represents a particularly difficult challenge in vaccine development, due to the inadequate immune response elicited against type B capsular polysaccharide. We have established an adult mouse intranasal challenge model for group B N. meningitidis to evaluate potential vaccine candidates through active immunization. Swiss Webster mice were inoculated intranasally with meningococci, and bacteria were recovered from the noses for at least 3 days postchallenge. Iron dextran was required in the bacterial inoculum to ensure sufficient meningococcal recovery from nasal tissue postchallenge. This model has been utilized to evaluate the potential of a recombinant lipidated group B meningococcal outer membrane protein P2086 (rLP2086) as a vaccine candidate. In this study, mice were immunized subcutaneously with purified rLP2086 formulated with or without an attenuated cholera toxin as an adjuvant. The mice were then challenged intranasally with N. meningitidis strain H355 or M982, and the colonization of nasal tissue was determined by quantitative culture 24 h postchallenge. We demonstrated that immunization with rLP2086 significantly reduced nasal colonization of mice challenged with the two different strains of group B N. meningitidis. Mice immunized with rLP2086 produced a strong systemic immunoglobulin G response, and the serum antibodies were cross-reactive with heterologous strains of group B N. meningitidis. The antibodies have functional activity against heterologous N. meningitidis strain, as demonstrated via bactericidal and infant rat protection assays. These results suggest that rLP2086 is a potential vaccine candidate for group B N. meningitidis.

scholarly journals Analysis of the role of TpUB05 antigen from Theileria parva in immune responses to malaria in humans compared to its homologue in Plasmodium falciparum; UB05 antigen

2019 ◽  
Author(s):  
Jerome Nyhalah Dinga ◽  
Stanley Dobgima Gamua ◽  
Stephanie Numenyi Perimbie ◽  
Francis N. G. Chuma ◽  
Dieudonné Lemuh Njimoh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Ex Vivo ◽  
Growth Inhibition Assay ◽  
Potential Marker ◽  
As Species ◽  
Potential Vaccine ◽  
First Time

Abstract Background: Despite the amount of resources deployed and technological advancements in Molecular Biology, vaccinology, immunology, genetics, and biotechnology, there is still no effective vaccines against malaria. Immunity to either malaria or East Coast fever is usually seen as species- and/or strain-specific. But there is growing body of evidence suggesting the possibility of the existence of cross strain, cross species and cross genus immune responses in apicomplexans. The principle of gene conservations indicates that homologues play similar role in closely related organisms. UB05 antigen (XP_001347656.2) from P. falciparum is part of chimeric UB05-09 antigen; a potential vaccine candidate has been demonstrated to be a marker of protective immunity in malaria. The homologue of UB05 in T. parva is TpUB05 (XP_763711.1) which was also tested and shown to be a potential marker of protective immunity in ECF as well. In a bid to identify potent markers of protective immunity to aid malaria vaccine development, TpUB05 was tested in malaria caused by P. falciparum . Results: It was observed that TpUB05 provoked stronger immune responses in malaria compared to UB05 antigen as tested using ELISA, ex-vivo ELISpot assay and in vitro growth inhibition assay. Conclusion: This study suggests for the first time that TpUB05 from T. parva is a better marker of protective immunity in malaria compared to its homologue UB05 from P. falciparum .

scholarly journals Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines

2022 ◽  
Vol 67 (4) ◽  
pp. 289-298
Author(s):  
Saad Alghamdi ◽  
Muhammad Umar Khayam Sahibzada ◽  
Nashwa T. Shesha ◽  
Akhmed Aslam ◽  
Ahmed Kabrah ◽  
...  
Keyword(s):  
Immune Responses ◽  
Pneumococcal Disease ◽  
Vaccine Candidate ◽  
Protein A ◽  
Surface Protein ◽  
Pneumococcal Infections ◽  
Promising Candidate ◽  
Host Immune Responses ◽  
Pneumococcal Surface Protein A ◽  
Potential Vaccine

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

scholarly journals Structure ofStreptococcus agalactiaeglyceraldehyde-3-phosphate dehydrogenase holoenzyme reveals a novel surface

2014 ◽  
Vol 70 (10) ◽  
pp. 1333-1339 ◽  
Author(s):  
Chapelle A. Ayres ◽  
Norbert Schormann ◽  
Olga Senkovich ◽  
Alexandra Fry ◽  
Surajit Banerjee ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Group B Streptococcus ◽  
Bacterial Pathogenesis ◽  
Bacterial Virulence ◽  
Significant Difference ◽  
Potential Vaccine ◽  
Group B

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a conserved cytosolic enzyme, which plays a key role in glycolysis. GAPDH catalyzes the oxidative phosphorylation of D-glyceraldehyde 3-phosphate using NAD or NADP as a cofactor. In addition, GAPDH localized on the surface of some bacteria is thought to be involved in macromolecular interactions and bacterial pathogenesis. GAPDH on the surface of group B streptococcus (GBS) enhances bacterial virulence and is a potential vaccine candidate. Here, the crystal structure of GBS GAPDH fromStreptococcus agalactiaein complex with NAD is reported at 2.46 Å resolution. Although the overall structure of GBS GAPDH is very similar to those of other GAPDHs, the crystal structure reveals a significant difference in the area spanning residues 294–307, which appears to be more acidic. The amino-acid sequence of this region of GBS GAPDH is also distinct compared with other GAPDHs. This region therefore may be of interest as an immunogen for vaccine development.

scholarly journals Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1843
Author(s):  
Connor A. P. Scott ◽  
Alberto A. Amarilla ◽  
Summa Bibby ◽  
Natalee D. Newton ◽  
Roy A. Hall ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Humoral Immunity ◽  
Vaccine Candidate ◽  
Serum Concentrations ◽  
Vaccine Candidates ◽  
Virus Maturation ◽  
Potential Safety ◽  
Increased Risk

The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epitopes on immature virions have been linked to increased ADE. We aimed to further understand the humoral immunity promoted by DENV particles of varying maturities in an AG129 mouse model using a chimeric insect specific vaccine candidate, bDENV-2. We immunized mice with mature, partially mature, and immature bDENV-2 and found that immunization with partially mature bDENV-2 produced more robust and cross-neutralizing immune responses than immunization with immature or mature bDENV-2. Upon challenge with mouse adapted DENV-2 (D220), we observed 80% protection for mature bDENV-2 vaccinated mice and 100% for immature and partially mature vaccinated mice, suggesting that protection to homotypic challenge is not dependent on maturation. Finally, we found reduced in vitro ADE at subneutralising serum concentrations for mice immunized with mature bDENV-2. These results suggest that both immature and mature DENV particles play a role in homotypic protection; however, the increased risk of in vitro ADE from immature particles indicates potential safety benefits from mature DENV-based vaccines.

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