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Article: Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand?

Al-Kassmy, Jawad / Pedersen, Jannie / Kobinger, Gary

Viruses. 2020 Aug. 07, v. 12, no. 8

2020

Abstract: Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the ... ...

Abstract	Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette–Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.
Keywords	COVID-19 infection ; DNA ; Middle East respiratory syndrome coronavirus ; Mycobacterium bovis BCG ; Severe acute respiratory syndrome coronavirus 2 ; Severe acute respiratory syndrome-related coronavirus ; clinical trials ; databases ; humans ; inactivated vaccines ; protein subunits ; vaccine development ; viruses ; China
Language	English
Dates of publication	2020-0807
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12080861
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand?

Al-Kassmy, Jawad / Pedersen, Jannie / Kobinger, Gary

Viruses

2020 Volume 12, Issue 8

Abstract	Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.
MeSH term(s)	Animals ; Betacoronavirus/immunology ; COVID-19 ; COVID-19 Vaccines ; Clinical Trials as Topic ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Humans ; Middle East Respiratory Syndrome Coronavirus/immunology ; Models, Animal ; Pandemics/prevention & control ; Pneumonia, Viral/immunology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome/immunology ; Severe Acute Respiratory Syndrome/prevention & control ; Severe Acute Respiratory Syndrome/virology ; Vaccines, DNA/immunology ; Viral Vaccines/administration & dosage ; Viral Vaccines/immunology
Chemical Substances	COVID-19 Vaccines ; Vaccines, DNA ; Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2020-08-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12080861
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand?

Al-Kassmy, Jawad / Pedersen, Jannie / Kobinger, Gary

Viruses

Abstract	Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #712882
Database	COVID19

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Article ; Online: Cell Culture Studies of the Efficacy and Barrier to Resistance of Sofosbuvir-Velpatasvir and Glecaprevir-Pibrentasvir against Hepatitis C Virus Genotypes 2a, 2b, and 2c.

Ramirez, Santseharay / Fernandez-Antunez, Carlota / Mikkelsen, Lotte S / Pedersen, Jannie / Li, Yi-Ping / Bukh, Jens

Antimicrobial agents and chemotherapy

2020 Volume 64, Issue 3

Abstract: The introduction of highly efficient therapies with direct-acting antivirals (DAA) for patients with chronic hepatitis C virus (HCV) infection offers exceptional opportunities to globally control this deadly disease. For achieving this ambitious goal, it ...

Abstract	The introduction of highly efficient therapies with direct-acting antivirals (DAA) for patients with chronic hepatitis C virus (HCV) infection offers exceptional opportunities to globally control this deadly disease. For achieving this ambitious goal, it is essential to prevent antiviral resistance against the most optimal first-line and retreatment DAA choices. We performed independent comparisons of the efficacy and barrier to resistance of pangenotypic DAA regimens for HCV genotype 2 infections, using previously and newly developed efficient cell culture-adapted strains of subtypes 2a, 2b, and 2c. With the applied experimental cell culture conditions, combination treatment with the sofosbuvir-velpatasvir or glecaprevir-pibrentasvir DAA regimen was efficient in eradicating HCV infections; in contrast, single-drug treatments frequently led to viral escape. Sequence analysis of drug targets from recovered viruses revealed known resistance-associated substitutions (RAS) emerging in the NS3 protease or NS5A after treatment failure. These RAS were genetically stable after viral passage, and viruses with these RAS exhibited significant phenotypic resistance. After sofosbuvir treatment failure, only a genotype 2a virus harbored NS5B RAS S282T and thus had decreased susceptibility to nucleotide analogs (nucs). However, in most cases, viral escape from sofosbuvir led to other NS5B substitutions but drug susceptibility was maintained, and in one case, no changes in NS5B were detected. For a genotype 2b virus, after treatment failure with sofosbuvir-velpatasvir, the efficacy of retreatment with glecaprevir-pibrentasvir was maintained due to the high barrier to resistance and low cross-resistance of pibrentasvir. Our findings suggest the slight superiority of glecaprevir-pibrentasvir against genotype 2b in culture, which could have potential therapeutic interest meriting more definitive investigations in the clinic.
MeSH term(s)	Antiviral Agents/pharmacology ; Benzimidazoles/pharmacology ; Carbamates/pharmacology ; Cell Line, Tumor ; Culture Media/chemistry ; Drug Combinations ; Drug Resistance, Viral/genetics ; Drug Therapy, Combination ; Gene Expression ; Genotype ; Hepacivirus/drug effects ; Hepacivirus/enzymology ; Hepacivirus/genetics ; Hepacivirus/isolation & purification ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/pathology ; Hepatitis C, Chronic/virology ; Hepatocytes/drug effects ; Hepatocytes/virology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Microbial Sensitivity Tests ; Mutation ; Pyrrolidines/pharmacology ; Quinoxalines/pharmacology ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Sofosbuvir/pharmacology ; Sulfonamides/pharmacology ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Antiviral Agents ; Benzimidazoles ; Carbamates ; Culture Media ; Drug Combinations ; Heterocyclic Compounds, 4 or More Rings ; NS3 protein, hepatitis C virus ; Pyrrolidines ; Quinoxalines ; RNA, Viral ; Sulfonamides ; Viral Nonstructural Proteins ; glecaprevir and pibrentasvir ; sofosbuvir-velpatasvir drug combination ; NS-5 protein, hepatitis C virus (EC 2.7.7.48) ; Sofosbuvir (WJ6CA3ZU8B)
Language	English
Publishing date	2020-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.01888-19
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Article: The First Assessments of Pediatric HBV Immunization Coverage in Mauritania and Persistence of Antibody Titers Post Infant Immunizations.

El Hachimi, Hala / El Alem, Mohamed Mahmoud Mohamed / Haimoudane, Esma / Yebouk, Cheikh / Pedersen, Jannie / Fall-Malick, F-Zahra / Khiddi, Fatimetou / Abdawe, Mohamed / Sadegh, Sidi Ahmed / Fausther-Bovendo, Hugues / Mohamed Abdellahi, Mohamed Vall

Vaccines

2023 Volume 11, Issue 3

Abstract: Background: The Hepatitis B virus (HBV) vaccine is used worldwide as an efficient tool to prevent the occurrence of chronic HBV infection and the subsequent liver disease. However, despite decades of vaccination campaigns, millions of new infections are ...

Abstract	Background: The Hepatitis B virus (HBV) vaccine is used worldwide as an efficient tool to prevent the occurrence of chronic HBV infection and the subsequent liver disease. However, despite decades of vaccination campaigns, millions of new infections are still reported every year. Here, we aimed to assess the nationwide HBV vaccination coverage in Mauritania as well as the presence of protective levels of the antibodies against HBV surface antigen (HBsAb) following vaccination in a sample of children immunized as infants. Methods: To evaluate the frequency of fully vaccinated and seroprotected children in Mauritania, a prospective serological study was conducted in the capital. First, we evaluated the pediatric HBV vaccine coverage in Mauritania between 2015 and 2020. Then, we examined the level of antibodies against HBV surface antigen (HBsAb) in 185 fully vaccinated children (aged 9 months to 12 years) by ELISA using the VIDAS hepatitis panel for Minividas (Biomerieux). These vaccinated children were sampled in 2014 or 2021. Results: In Mauritania, between 2016 and 2019, more than 85% of children received the complete HBV vaccine regimen. While 93% of immunized children between 0 and 23 months displayed HBsAb titer >10 IU/L, the frequency of children with similar titers decreased to 63, 58 and 29% in children aged between 24-47, 48-59 and 60-144 months, respectively. Conclusions: A marked reduction in the frequency of HBsAb titer was observed with time, indicating that HBsAb titer usefulness as marker of protection is short lived and prompting the need for more accurate biomarkers predictive of long-term protection.
Language	English
Publishing date	2023-03-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11030588
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV.

Azizi, Hiva / Knapp, Jason P / Li, Yue / Berger, Alice / Lafrance, Marc-Alexandre / Pedersen, Jannie / de la Vega, Marc-Antoine / Racine, Trina / Kang, Chil-Yong / Mann, Jamie F S / Dikeakos, Jimmy D / Kobinger, Gary / Arts, Eric J

Vaccines

2023 Volume 11, Issue 5

Abstract: Vesicular stomatitis virus (VSV) remains an attractive platform for a potential HIV-1 vaccine but hurdles remain, such as selection of a highly immunogenic HIV-1 Envelope (Env) with a maximal surface expression on recombinant rVSV particles. An HIV-1 Env ...

Abstract	Vesicular stomatitis virus (VSV) remains an attractive platform for a potential HIV-1 vaccine but hurdles remain, such as selection of a highly immunogenic HIV-1 Envelope (Env) with a maximal surface expression on recombinant rVSV particles. An HIV-1 Env chimera with the transmembrane domain (TM) and cytoplasmic tail (CT) of SIVMac239 results in high expression on the approved Ebola vaccine, rVSV-ZEBOV, also harboring the Ebola Virus (EBOV) glycoprotein (GP). Codon-optimized (CO) Env chimeras derived from a subtype A primary isolate (A74) are capable of entering a CD4+/CCR5+ cell line, inhibited by HIV-1 neutralizing antibodies PGT121, VRC01, and the drug, Maraviroc. The immunization of mice with the rVSV-ZEBOV carrying the CO A74 Env chimeras results in anti-Env antibody levels as well as neutralizing antibodies 200-fold higher than with the NL4-3 Env-based construct. The novel, functional, and immunogenic chimeras of CO A74 Env with the SIV_Env-TMCT within the rVSV-ZEBOV vaccine are now being tested in non-human primates.
Language	English
Publishing date	2023-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11050977
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Article ; Online: Transient Liver Damage and Hemolysis Are Associated With an Inhibition of Ebola Virus Glycoprotein-Specific Antibody Response and Lymphopenia.

Fausther-Bovendo, Hugues / Qiu, Xiangguo / Babuadze, George Giorgi / Azizi, Hiva / Pedersen, Jannie / Wong, Gary / Kobinger, Gary P

The Journal of infectious diseases

2021 Volume 225, Issue 10, Page(s) 1852–1855

Abstract: Numerous studies have demonstrated the importance of the adaptive immunity for survival following Ebola virus (EBOV) infection. To evaluate the contribution of tissue damage to EBOV-induced immune suppression, acute liver damage or hemolysis, 2 symptoms ... ...

Abstract	Numerous studies have demonstrated the importance of the adaptive immunity for survival following Ebola virus (EBOV) infection. To evaluate the contribution of tissue damage to EBOV-induced immune suppression, acute liver damage or hemolysis, 2 symptoms associated with lethal EBOV infection, were chemically induced in vaccinated mice. Results show that either liver damage or hemolysis was sufficient to inhibit the host humoral response against EBOV glycoprotein and to drastically reduce the level of circulating T cells. This study thus provides a possible mechanism for the limited specific antibody production and lymphopenia in individuals with lethal hemorrhagic fever infections.
MeSH term(s)	Animals ; Antibodies, Viral ; Antibody Formation ; Ebolavirus ; Glycoproteins ; Hemolysis ; Hemorrhagic Fever, Ebola/immunology ; Liver/pathology ; Liver/virology ; Lymphopenia/virology ; Mice
Chemical Substances	Antibodies, Viral ; Glycoproteins
Language	English
Publishing date	2021-11-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiab552
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Article: An Adaptable Platform for in-house Hepatitis C Serology

Pedersen, Jannie / Moukandja, Irène Pegha / Ndidi, Stella / Sørensen, Anna-Louise / Koumakpayi, Ismaël Hervé / Lekana-Douki, Jean-Bernard / Vachon, Marie-Louise / Weis, Nina / Kobinger, Gary / Fausther-Bovendo, Hugues

Journal of virological methods. 2022 July 14,

2022

Abstract: Serology-based diagnosis remains one of the major tools for diagnosis and surveillance of infectious diseases. However, for many neglected diseases no or only few commercial assays are available and often with prices prohibiting large scale testing in ... ...

Abstract	Serology-based diagnosis remains one of the major tools for diagnosis and surveillance of infectious diseases. However, for many neglected diseases no or only few commercial assays are available and often with prices prohibiting large scale testing in low and middle-income countries (LMICs). We developed an adaptable enzyme-linked immunoassay (ELISA) using hepatitis C virus (HCV) as a proof-of-concept application. By combining the maltose-binding-protein with a multiepitope HCV protein, we were able to obtain a high concentration of protein suitable for downstream applications. Following optimization, the assay was verified using previously tested human samples from Canada, Denmark and Gabon in parallel with the use of a commercial protein. Sensitivity and specificity were calculated to 98% and 97% respectively, after accounting for non-specific binding and assay optimization. This study provides a thorough description of the development, and validation of a multiepitope ELISA-based diagnostic assay against HCV, which could be implemented at low cost. The described methodology can be readily adapted to develop novel ELISA-based diagnostic assays for other infectious pathogens with well-described immunogenic epitopes. This method could improve the diagnosis of neglected diseases for which affordable diagnostic assays are lacking.
Keywords	Hepatitis C virus ; enzyme-linked immunosorbent assay ; epitopes ; hepatitis C ; humans ; monitoring ; serology ; Canada ; Denmark ; Gabon
Language	English
Dates of publication	2022-0714
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2022.114586
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An adaptable platform for in-house hepatitis C serology.

Journal of virological methods

2022 Volume 308, Page(s) 114586

Abstract	Serology-based diagnosis remains one of the major tools for diagnosis and surveillance of infectious diseases. However, for many neglected diseases no or only few commercial assays are available and often with prices prohibiting large scale testing in low and middle-income countries (LMICs). We developed an adaptable enzyme-linked immunoassay (ELISA) using hepatitis C virus (HCV) as a proof-of-concept application. By combining the maltose-binding-protein with a multiepitope HCV protein, we were able to obtain a high concentration of protein suitable for downstream applications. Following optimization, the assay was verified using previously tested human samples from Canada, Denmark and Gabon in parallel with the use of a commercial protein. Sensitivity and specificity were calculated to 98 % and 97 % respectively, after accounting for non-specific binding and assay optimization. This study provides a thorough description of the development, and validation of a multiepitope ELISA-based diagnostic assay against HCV, which could be implemented at low cost. The described methodology can be readily adapted to develop novel ELISA-based diagnostic assays for other infectious pathogens with well-described immunogenic epitopes. This method could improve the diagnosis of neglected diseases for which affordable diagnostic assays are lacking.
MeSH term(s)	Enzyme-Linked Immunosorbent Assay/methods ; Hepacivirus ; Hepatitis C/diagnosis ; Hepatitis C Antibodies ; Hepatitis C Antigens ; Humans ; Neglected Diseases ; Sensitivity and Specificity
Chemical Substances	Hepatitis C Antibodies ; Hepatitis C Antigens
Language	English
Publishing date	2022-07-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2022.114586
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Article: Impact of Recombinant VSV-HIV Prime, DNA-Boost Vaccine Candidates on Immunogenicity and Viremia on SHIV-Infected Rhesus Macaques.

Berger, Alice / Pedersen, Jannie / Kowatsch, Monika M / Scholte, Florine / Lafrance, Marc-Alexandre / Azizi, Hiva / Li, Yue / Gomez, Alejandro / Wade, Matthew / Fausther-Bovendo, Hugues / de La Vega, Marc-Antoine / Jelinski, Joseph / Babuadze, George / Nepveu-Traversy, Marie-Edith / Lamarre, Claude / Racine, Trina / Kang, Chil-Yong / Gaillet, Bruno / Garnier, Alain /

Gilbert, Rénald / Kamen, Amine / Yao, Xiao-Jian / Fowke, Keith R / Arts, Eric / Kobinger, Gary

Vaccines

2024 Volume 12, Issue 4

Abstract: Currently, no effective vaccine to prevent human immunodeficiency virus (HIV) infection is available, and various platforms are being examined. The vesicular stomatitis virus (VSV) vaccine vehicle can induce robust humoral and cell-mediated immune ... ...

Abstract	Currently, no effective vaccine to prevent human immunodeficiency virus (HIV) infection is available, and various platforms are being examined. The vesicular stomatitis virus (VSV) vaccine vehicle can induce robust humoral and cell-mediated immune responses, making it a suitable candidate for the development of an HIV vaccine. Here, we analyze the protective immunological impacts of recombinant VSV vaccine vectors that express chimeric HIV Envelope proteins (Env) in rhesus macaques. To improve the immunogenicity of these VSV-HIV Env vaccine candidates, we generated chimeric Envs containing the transmembrane and cytoplasmic tail of the simian immunodeficiency virus (SIV), which increases surface Env on the particle. Additionally, the Ebola virus glycoprotein was added to the VSV-HIV vaccine particles to divert tropism from CD4 T cells and enhance their replications both in vitro and in vivo. Animals were boosted with DNA constructs that encoded matching antigens. Vaccinated animals developed non-neutralizing antibody responses against both the HIV Env and the Ebola virus glycoprotein (EBOV GP) as well as systemic memory T-cell activation. However, these responses were not associated with observable protection against simian-HIV (SHIV) infection following repeated high-dose intra-rectal SHIV SF162p3 challenges.
Language	English
Publishing date	2024-03-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12040369
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