Dataset Information

Virus Like Particles (VLP) as multivalent vaccine candidate against Chikungunya, Japanese Encephalitis, Yellow Fever and Zika Virus.

ABSTRACT: Mosquito borne viral diseases are an emerging threat as evident from the recent outbreak of Zika virus (ZIKV) as well as repeated outbreaks of Chikungunya (CHIKV), Yellow fever (YFV) and Japanese encephalitis (JEV) virus in different geographical regions. These four arboviruses are endemic in overlapping regions due to the co-prevalence of the transmitting mosquito vector species Aedes and Culex. Thus, a multivalent vaccine that targets all four viruses would be of benefit to regions of the world where these diseases are endemic. We developed a potential Virus Like Particle (VLP) based multivalent vaccine candidate to target these diseases by using stable cell lines that continuously secrete VLPs in the culture supernatants. Moreover, inclusion of Capsid in the VLPs provides an additional viral protein leading to an enhanced immune response as evident from our previous studies with ZIKV. Immunization of Balb/c mice with different combinations of Capsid protein containing VLPs either as monovalent, bivalent or tetravalent formulation resulted in generation of high levels of neutralizing antibodies. Interestingly, the potential tetravalent VLP vaccine candidate provided strong neutralizing antibody titers against all four viruses. The 293?T stable cell lines secreting VLPs were adapted to grow in suspension cultures to facilitate vaccine scale up. Our stable cell lines secreting individual VLPs provide a flexible yet scalable platform conveniently adaptable to different geographical regions as per the need. Further studies in appropriate animal models will be needed to define the efficacy of the multivalent vaccine candidate to protect against lethal virus challenge.

SUBMITTER: Garg H

PROVIDER: S-EPMC7055223 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Virus Like Particles (VLP) as multivalent vaccine candidate against Chikungunya, Japanese Encephalitis, Yellow Fever and Zika Virus.

Garg Himanshu H Mehmetoglu-Gurbuz Tugba T Joshi Anjali A

Scientific reports 20200304 1

Mosquito borne viral diseases are an emerging threat as evident from the recent outbreak of Zika virus (ZIKV) as well as repeated outbreaks of Chikungunya (CHIKV), Yellow fever (YFV) and Japanese encephalitis (JEV) virus in different geographical regions. These four arboviruses are endemic in overlapping regions due to the co-prevalence of the transmitting mosquito vector species Aedes and Culex. Thus, a multivalent vaccine that targets all four viruses would be of benefit to regions of the worl ...[more]

PMID: 32132648

Similar Datasets

Project description:BackgroundComplex patterns of cross-reactivity exist between flaviviruses, yet there is no precise understanding of how sequential exposures due to flavivirus infections or vaccinations impact subsequent antibody responses.MethodsWe investigated whether B cell priming from Japanese encephalitis virus (JEV) or yellow fever virus (YFV) vaccination impacted binding and functional antibody responses to flaviviruses following vaccination with a Zika virus (ZIKV) purified inactivated virus (ZPIV) vaccine. Binding antibody responses and Fc gamma receptor engagement against 23 flavivirus antigens were characterized along with neutralization titres and Fc effector responses in 75 participants at six time points.FindingsWe found no evidence that priming with JEV or YFV vaccines improved the magnitude of ZPIV induced antibody responses to ZIKV. Binding antibodies and Fc gamma receptor engagement to ZIKV antigens did not differ significantly across groups, while antibody-dependent cellular phagocytosis (ADCP) and neutralizing responses were higher in the naïve group than in the JEV and YFV primed groups following the second ZPIV immunization (p ≤ 0.02). After a third dose of ZPIV, ADCP responses remained higher in the naïve group than in the primed groups. However, priming affected the quality of the response following ZPIV vaccination, as primed individuals recognized a broader array of flavivirus antigens than individuals in the naïve group.InterpretationWhile a priming vaccination to either JEV or YFV did not boost ZIKV-specific responses upon ZIKV vaccination, the qualitatively different responses elicited in the primed groups highlight the complexity in the cross-reactive antibody responses to flaviviruses.FundingThis work was supported by a cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of the Army [W81XWH-18-2-0040]. The work was also funded in part by the National Institute of Allergy and Infectious Diseases (NIAID) R01AI155983 to SJK and KM.

Project description:Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being unprepared against future YFV epidemics. Here we report that a live attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D-mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific nonneutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV nonstructural (NS) proteins. Our findings reveal the potential of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev, could confer protection against two flaviviruses. This dual protection may have implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev may already be protected against YFV should outbreaks ever occur on that continent, as several countries/regions in the Asia-Pacific are vulnerable to international spread of the YFV.IMPORTANCE Efficient and safe vaccines against yellow fever (e.g., YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses exist. However, the vaccine supply cannot cope with an increasing demand posed by urban outbreaks in recent years. Here we report that JE-CVax/Imojev, a YFV-17D-based chimeric Japanese encephalitis vaccine, also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev may be considered. Moreover, wider use of JE-CVax/Imojev in Asia may lower the risk of the much-feared YFV spillover to the continent. More generally, chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses may be considered dual vaccines for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection (inherent to current dengue vaccines and dengue vaccine candidates) could be designed.

Dataset Information

Virus Like Particles (VLP) as multivalent vaccine candidate against Chikungunya, Japanese Encephalitis, Yellow Fever and Zika Virus.

Publications

Virus Like Particles (VLP) as multivalent vaccine candidate against Chikungunya, Japanese Encephalitis, Yellow Fever and Zika Virus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets