Zika virus-like particle (VLP) based vaccine

Boigard, Hélène; Alimova, Alexandra; Martin, George R.; Katz, A.; Gottlieb, Paul; Galarza, Jose M.

doi:10.1371/journal.pntd.0005608

Cited by 133 publications

(113 citation statements)

References 41 publications

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“…Flavivirus prM protein typically associates with E to form heterodimers and is important for proper folding of E [13][14][15][16] . Co-expression of prM and E of several flaviviruses including ZIKV results in the secretion of virus-like particles (VLPs) termed recombinant subviral particles [17][18][19] . The prM protein is an integral part of both virions and subviral particles, and undergoes a cleavage event during virus maturation 20 .…”

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confidence: 99%

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

et al. 2018

Nat Commun

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Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.

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confidence: 99%

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

et al. 2018

Nat Commun

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“…Studies have demonstrated an effective neutralizing antibody response capable of protecting against ZIKV infection in both mice and nonhuman primates (20)(21)(22), leading to several clinical trials that are under way (ClinicalTrials.gov identifiers NCT02963909, NCT02840487, NCT02887482, NCT02809443, and NCT02952833). While virus-like particle (VLP)-based vaccines have been tested for nearly all flaviviruses, a VLP-based approach for ZIKV was only recently described (27) and needs further testing. One of the pros with the development of a ZIKV vaccine is that even though the virus exists as two distinct lineages (African and Asian/American) (28), the immune response generated against the virus is broadly protective (29), thus obviating the need to incorporate different serotypes in the vaccine.…”

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confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

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Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (CprM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.KEYWORDS C-prM-E, diagnostics, microneutralization, neutralization, PRNT, reporter, reporter virus particles, vaccine, Zika, prM-E S ince the identification of Zika virus (ZIKV) from a rhesus monkey in Uganda in 1947 (1, 2) until 2010, the virus predominantly circulated between Aedes mosquitoes and nonhuman primates. Periodic episodes were inde...

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“…In addition, our group has successfully adopted the same adjuvant formulation with AddaVax for an investigational VLP-based vaccine against Zika Virus (ZIKV). Mice immunized with ZIK-VLPs developed very high titers of neutralizing antibodies [105]. …”

Section: Classes Of Adjuvants Tested For Vlp-based Vaccinesmentioning

confidence: 99%

Adjuvant formulations for virus-like particle (VLP) based vaccines

Cimica

Galarza

2017

Clinical Immunology

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102

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The development of virus-like particle (VLP) technology has had an enormous impact on modern vaccinology. In order to optimize the efficacy and safety of VLP-based vaccines, adjuvants are included in most vaccine formulations. To date, most licensed VLP-based vaccines utilize the classic aluminum adjuvant compositions. Certain challenging pathogens and weak immune responder subjects may require further optimization of the adjuvant formulation to maximize the magnitude and duration of the protective immunity. Indeed, novel classes of adjuvants such as liposomes, agonists of pathogen recognition receptors, polymeric particles, emulsions, cytokines and bacterial toxins, can be used to optimize the immunostimulatory activity of a VLP-based vaccine. This review describes the current advances in adjuvant technology for VLP-based vaccines directed at viral diseases, and discusses the basic principles for designing adjuvant formulations for enhancing the vaccine immunogenicity.

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Zika virus-like particle (VLP) based vaccine

Cited by 133 publications

References 41 publications

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Adjuvant formulations for virus-like particle (VLP) based vaccines

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