Virus-like particles produced in Saccharomyces cerevisiae elicit protective immunity against Coxsackievirus A16 in mice

Zhao, Hui; Li, Hao-Yang; Han, Jianfeng; Deng, Yong-Qiang; Li, Yuexiang; Zhu, Shun-Ya; Qin, E-De; Chen, Rong; Qin, Cheng‐Feng

doi:10.1007/s00253-013-5257-3

Cited by 41 publications

(37 citation statements)

References 36 publications

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“…168 Virus-like particles (VLP) produced in Saccharomyces cervisiae have also elicited potent neutralizing responses and passive transfer of immune sera protected neonate mice against lethal CV-A16 challenge. 169 Combination of inactivated EV-A71/CV-A16 vaccines formulated in alum 170 or with PELC/CpG 171 elicited balanced neutralizing responses against both viruses whereas monovalent CV-A16 vaccines did not protect against EV-A71 infection. Furthermore, maternal immunization of mice with the bivalent vaccine protected neonates challenged with the mouse-adapted EV-A71/MVA-N strain and the clinical isolate CV-A16/G08.…”

Section: Development Of a Bivalent Ev-a71/cv-a16 Vaccinementioning

confidence: 99%

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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Keywords: bivalent and multivalent vaccines, coxsackievirus A16, coxsackieviruses B3 and B5, echovirus 30, epidemiology, enterovirus A (EV-A), enterovirus A71, hand, foot and mouth diseases, inactivated whole virion vaccines, monovalent, EV-A71 vaccine Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

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Section: Development Of a Bivalent Ev-a71/cv-a16 Vaccinementioning

confidence: 99%

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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“…Currently, several experimental CVA16 and EV71 vaccines are under development, including inactivated CVA16, [23][24][25] and CVA16 VLPs derived from insect cells 26 and Saccharomyces cerevisiae. 27 Among these, the EV71 inactivated vaccine has been evaluated and passed through a phase III clinical trial, while the development of EV71 VLPs in insect cells and S. cerevisiae is still ongoing. 28,29 However, until now these vaccines have not been evaluated in bivalent composition.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of monovalent and bivalent vaccines against lethalEnterovirus71 andCoxsackievirusA16 infection in newborn mice

Sun

Jiang

Liang

et al. 2014

Human Vaccines & Immunotherapeutics

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Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) have caused severe epidemics of hand, foot and mouth disease (HFMD) in the Asia Pacific in recent years, particularly in infants and young children. This disease has become a serious public health problem, as no vaccines or antiviral drugs have been approved for EV71 and CA16 infections. In this study, we compared four monovalent vaccines, including formalin-inactivated EV71 virus (iEV71), EV71 virus-like particles (VLPs) (vEV71), formalin-inactivated CVA16 virus (iCVA16) and CVA16 VLPs (vCVA16), along with two bivalent vaccines, including equivalent doses of formalin-inactivated EV71CCVA16 virus (iEV71CiCVA16) and EV71CCVA16 VLPs (vEV71CvCVA16). The IgG titers and neutralization antibodies titers demonstrated that there are no immune interference exists between the two immunogens of EV71 and CVA16. IgG subclass isotyping revealed that IgG1 and IgG2b were induced primarily in all vaccine groups. Furthermore, cross-neutralization antibodies were elicited in mouse sera against other sub-genotypes of EV71 and CVA16. In vivo challenge experiments showed that the immune sera from vaccinated animals could confer passive protection to newborn mice against lethal challenge with 14 LD 50 of EV71 and 50 LD 50 of CVA16. Our results indicated that bivalent vaccination is promising for HFMD vaccine development. With the advantage of having a better safety profile than inactivated virus vaccines, VLPs should be used to combine both EV71 and CVA16 antigens as a candidate vaccine for prevention of HFMD virus transmission.

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“…Various candidates against EV71 or CA16 virus, including inactivated vaccines (3,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), live attenuated vaccines (23,24), subunit vaccines based on the VP1 protein (25), virus-like particle (VLP) vaccines (26)(27)(28)(29)(30)(31)(32)(33)(34), and epitopebased vaccines (35)(36)(37)(38)(39), were shown to possess various levels of efficacy in animal studies or human clinical trials. In particular, inactivated EV71 vaccines showed promising results against EV71-associated diseases in recent phase 3 clinical studies conducted in mainland China (20)(21)(22).…”

mentioning

confidence: 99%

“…Both EV71 and CA16 VLPs consist of 60 copies for each of the capsid proteins, VP0, VP1, and VP3, which follow a P ϭ 3 icosahedral arrangement. Previous studies showed that both EV71 and CA16 VLPs can elicit potent immune responses and are able to protect immunized mice against lethal challenges with EV71 or CA16 virus (27,31,33,34). How VLP vaccines mimic their viral counterparts structurally and how the neutralizing epitopes are preserved on the surface of VLPs are issues of big interest for effective vaccine development.…”

mentioning

confidence: 99%

Cryo-Electron Microscopy Study of Insect Cell-Expressed Enterovirus 71 and Coxsackievirus A16 Virus-Like Particles Provides a Structural Basis for Vaccine Development

Gong

Zhu

Zhou

et al. 2014

J Virol

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Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with occasional severe neurological complications. A number of vaccine candidates against EV71 or CA16 have been reported; however, no vaccine is currently available for clinical use. Here, we generated a secreted version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect cell expression system and reconstructed the three-dimensional (3D) structures of both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-Å and 5.5-Å resolutions, respectively. The reconstruction results showed that the cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published crystal structures for EV71 natural empty particles and CA16 135S-like expanded particles, respectively. Our cryo-EM analysis also revealed that the majority of previously identified linear neutralizing epitopes are well preserved on the surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce efficiently neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71-and CA16-associated HFMD. IMPORTANCEThe recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common etiological agents responsible for HFMD. In this paper, we show that secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell expression system highly resemble the crystal structures of their viral conterparts and that the majority of previously identified linear neutralizing epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs can efficiently induce neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71-and CA16-associated HFMD. Hand, foot, and mouth disease (HFMD) most frequently occurs in infants or children under 5 years old. Although most cases are mild and self-limited, HFMD can in some cases cause severe symptoms, such as myocarditis, pulmonary edema, and central nervous system complications ranging from flaccid paralysis to fatal encephalitis (1, 2). The recent epidemics of HFMD led to serious public health threats in the Asia Pacific region. In China, 1.16 million and 1.77 million cases of HFMD, including 353 and 905 deaths, were reported for 2009 and 2010, respectively (3). Etiologic studies revealed that enteroviruses, especially enterovirus 71 (EV71) and coxsackievirus A16 (CA16), are the most common causative agents responsible for HFMD epidemics (4-6). A clinical survey of the...

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Virus-like particles produced in Saccharomyces cerevisiae elicit protective immunity against Coxsackievirus A16 in mice

Cited by 41 publications

References 36 publications

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Evaluation of monovalent and bivalent vaccines against lethalEnterovirus71 andCoxsackievirusA16 infection in newborn mice

Cryo-Electron Microscopy Study of Insect Cell-Expressed Enterovirus 71 and Coxsackievirus A16 Virus-Like Particles Provides a Structural Basis for Vaccine Development

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