scholarly journals Ebola Virus Glycoprotein Domains Associated with Protective Efficacy

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 630
Author(s):  
Bharti Bhatia ◽  
Wakako Furuyama ◽  
Thomas Hoenen ◽  
Heinz Feldmann ◽  
Andrea Marzi
Keyword(s):  
Immune Response ◽  
Ebola Virus ◽  
Immune Cell ◽  
Protective Efficacy ◽  
West African ◽  
Protective Immune Response ◽  
Hemorrhagic Disease ◽  
Base Vector ◽  
Vesicular Stomatitis ◽  
Human Use

Ebola virus (EBOV) is the cause of sporadic outbreaks of human hemorrhagic disease in Africa, and the best-characterized virus in the filovirus family. The West African epidemic accelerated the clinical development of vaccines and therapeutics, leading to licensure of vaccines and antibody-based therapeutics for human use in recent years. The most widely used vaccine is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) (VSV-EBOV). Due to its favorable immune cell targeting, this vaccine has also been used as a base vector for the development of second generation VSV-based vaccines against Influenza, Nipah, and Zika viruses. However, in these situations, it may be beneficial if the immunogenicity against EBOV GP is minimized to induce a better protective immune response against the other foreign immunogen. Here, we analyzed if EBOV GP can be truncated to be less immunogenic, yet still able to drive replication of the vaccine vector. We found that the EBOV GP glycan cap and the mucin-like domain are both dispensable for VSV-EBOV replication. The glycan cap, however, appears critical for mediating a protective immune response against lethal EBOV challenge in mice.

scholarly journals Ebola virus glycoprotein domains associated with protective efficacy

2021 ◽  
Author(s):  
Bharti Bhatia ◽  
Wakako Furuyama ◽  
Thomas Hoenen ◽  
Heinz Feldmann ◽  
Andrea Marzi
Keyword(s):  
Immune Response ◽  
Ebola Virus ◽  
Immune Cell ◽  
Protective Efficacy ◽  
Protective Immune Response ◽  
Hemorrhagic Disease ◽  
The West ◽  
Base Vector ◽  
Vesicular Stomatitis ◽  
Human Use

Ebola virus (EBOV) is the cause of sporadic outbreaks of human hemorrhagic disease in Africa, and the best-characterized virus in the filovirus family. The West Africa epidemic accelerated the clinical development of vaccines and therapeutics leading to licensure of vaccines and antibody-based therapeutics for human use in recent years. The most widely used vaccine is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP)(VSV-EBOV). Due to its favorable immune cell targeting, this vaccine has also been used as base-vector for the development of second generation VSV-based vaccines against Influenza, Nipah, and Zika viruses. However, in these situations it may be beneficial if the immunogenicity against EBOV GP is minimized to induce a better protective immune response against the other foreign immunogen. Here, we analyzed if EBOV GP can be truncated to be less immunogenic yet still able to drive replication of the vaccine vector. We found that the EBOV GP glycan cap and the mucin-like domain are both dispensable for VSV-EBOV replication. The glycan cap domain, however, appears critical for mediating a protective immune response against lethal EBOV challenge in mice.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2020 ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Past Infection ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Membrane Antigens ◽  
Human Use

Abstract Background: Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods: In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results: We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions: The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Post Treatment ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Membrane Antigens ◽  
Human Use

Abstract Background Visceral leishmaniasis (VL), is a parasitic disease that causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, a test of cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens (LAg), were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six months post-treatment patients. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72 and 91 kDa proteins. Results We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post-treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa proteins are efficient in diagnosis, whereas 72 and 91 kDa proteins may be used to monitor treatment outcome. In another assay, 51 and 63 kDa proteins demonstrated maximum ability to upregulate IFN-γ and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa proteins demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell-mediated immune response, suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access the long-term immune response.

scholarly journals Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses

2015 ◽  
Vol 90 (1) ◽  
pp. 266-278 ◽  
Author(s):  
Frederick W. Holtsberg ◽  
Sergey Shulenin ◽  
Hong Vu ◽  
Katie A. Howell ◽  
Sonal J. Patel ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Rational Design ◽  
Ebola Virus ◽  
Immune Cell ◽  
Virus Disease ◽  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
Cross Reactivity ◽  
Virus Species

ABSTRACTThe unprecedented 2014-2015 Ebola virus disease (EVD) outbreak in West Africa has highlighted the need for effective therapeutics against filoviruses. Monoclonal antibody (MAb) cocktails have shown great potential as EVD therapeutics; however, the existing protective MAbs are virus species specific. Here we report the development of pan-ebolavirus and pan-filovirus antibodies generated by repeated immunization of mice with filovirus glycoproteins engineered to drive the B cell responses toward conserved epitopes. Multiple pan-ebolavirus antibodies were identified that react to the Ebola, Sudan, Bundibugyo, and Reston viruses. A pan-filovirus antibody that was reactive to the receptor binding regions of all filovirus glycoproteins was also identified. Significant postexposure efficacy of several MAbs, including a novel antibody cocktail, was demonstrated. For the first time, we report cross-neutralization andin vivoprotection against two highly divergent filovirus species, i.e., Ebola virus and Sudan virus, with a single antibody. Competition studies indicate that this antibody targets a previously unrecognized conserved neutralizing epitope that involves the glycan cap. Mechanistic studies indicated that, besides neutralization, innate immune cell effector functions may play a role in the antiviral activity of the antibodies. Our findings further suggest critical novel epitopes that can be utilized to design effective cocktails for broad protection against multiple filovirus species.IMPORTANCEFiloviruses represent a major public health threat in Africa and an emerging global concern. Largely driven by the U.S. biodefense funding programs and reinforced by the 2014 outbreaks, current immunotherapeutics are primarily focused on a single filovirus species called Ebola virus (EBOV) (formerly Zaire Ebola virus). However, other filoviruses including Sudan, Bundibugyo, and Marburg viruses have caused human outbreaks with mortality rates as high as 90%. Thus, cross-protective immunotherapeutics are urgently needed. Here, we describe monoclonal antibodies with cross-reactivity to several filoviruses, including the first report of a cross-neutralizing antibody that exhibits protection against Ebola virus and Sudan virus in mice. Our results further describe a novel combination of antibodies with enhanced protective efficacy. These results form a basis for further development of effective immunotherapeutics against filoviruses for human use. Understanding the cross-protective epitopes are also important for rational design of pan-ebolavirus and pan-filovirus vaccines.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2020 ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Past Infection ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Membrane Antigens ◽  
Human Use

Abstract Background Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, humans PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results We found that 34 and 51 kDa fractions show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

scholarly journals Progress in Elucidating Potential Markers and Mechanisms of Rapid Protection Conferred by the VSV-Vectored Ebola Virus Vaccine

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Gary Wong
Keyword(s):  
Immune Response ◽  
Ebola Virus ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Host Responses ◽  
Research Progress ◽  
Lethal Challenge ◽  
Adaptive Immune ◽  
Vesicular Stomatitis ◽  
Vectored Vaccine

ABSTRACT Research progress over the past 20 years has yielded several experimental Ebola virus (EBOV) vaccine candidates, which were shown to be effective in nonhuman primates when given 28 days before a lethal challenge. Of these, the vesicular stomatitis virus (VSV)-vectored vaccine against EBOV (VSV-EBOV) is unique at being able to induce rapid protection, with 100% survival achieved as soon as 7 days after EBOV challenge. In a recent mBio article, Menicucci et al. carried out a transcriptome analysis of host responses in monkeys immunized with VSV-EBOV from 28 to 3 days before challenge (A. R. Menicucci, A. Jankeel, H. Feldmann, A. Marzi, and I. Messaoudi, mBio 10:e00597-19, 2019, https://doi.org/10.1128/mBio.00597-19). It was found that surviving animals had a controlled innate immune response coupled with rapid adaptive immunity, but this was not detected in nonsurviving animals. These studies highlight the important role innate immunity plays in creating an antiviral state to restrict EBOV replication and ensuring enough time for the vaccine to induce an effective adaptive immune response.

scholarly journals Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine

mBio ◽  
2022 ◽  
Author(s):  
Wakako Furuyama ◽  
Kyle Shifflett ◽  
Amanda N. Pinski ◽  
Amanda J. Griffin ◽  
Friederike Feldmann ◽  
...  
Keyword(s):  
Single Dose ◽  
Vesicular Stomatitis Virus ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
European Medicines Agency ◽  
Vaccine Platform ◽  
Vesicular Stomatitis ◽  
Deadly Disease ◽  
Human Use ◽  
The U.S

The vesicular stomatitis virus (VSV) vaccine platform rose to fame in 2019, when a VSV-based Ebola virus (EBOV) vaccine was approved by the European Medicines Agency and the U.S. Food and Drug Administration for human use against the deadly disease.

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