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Ku Z.,CAS Shanghai Institutes for Biological Sciences | Liu Q.,CAS Shanghai Institutes for Biological Sciences | Ye X.,CAS Shanghai Institutes for Biological Sciences | Cai Y.,CAS Shanghai Institutes for Biological Sciences | And 6 more authors.
Vaccine | Year: 2014

Enterovirus 71(EV71) and coxsackievirus A16 (CA16) are responsible for hand, foot and mouth disease which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Co-circulation of and co-infection by both viruses underscores the importance and urgency of developing vaccines against both viruses simultaneously. Here we report the immunogenicity and protective efficacy of a bivalent combination vaccine comprised of EV71 and CA16 virus-like particles (VLPs). We show that monovalent EV71- or CA16-VLPs-elicited serum antibodies exhibited potent neutralization effect on the homotypic virus but little or no effect on the heterotypic one, whereas the antisera against the bivalent vaccine formulation were able to efficiently neutralize both EV71 and CA16, indicating there is no immunological interference between the two antigens with respect to their ability to induce virus-specific neutralizing antibodies. Passive immunization with monovalent VLP vaccines protected mice against a homotypic virus challenge but not heterotypic infection. Surprisingly, antibody-dependent enhancement (ADE) of disease was observed in mice passively transferred with mono-specific anti-CA16 VLP sera and subsequently challenged with EV71. In contrast, the bivalent VLP vaccine conferred full protection against lethal challenge by either EV71 or CA16, thus eliminating the potential of ADE. Taken together, our results demonstrate for the first time that the bivalent VLP approach represents a safe and efficacious vaccine strategy for both EV71 and CA16. © 2014 Elsevier Ltd.


Sun L.,CAS Institute of Process Engineering | Xiong Z.,CAS Institute of Process Engineering | Xiong Z.,University of Chinese Academy of Sciences | Zhou W.,CAS Institute of Process Engineering | And 7 more authors.
Biochemical Engineering Journal | Year: 2015

A new type of microcarrier was prepared for anchorage-dependent animal cell culture. Similar to the commercial product Cytodex 1, the newcomer is also spherical in micro-size range with ionic group DEAE, but the matrix is konjac glucomannan (KGM) from a natural plant. The optimal anion exchange capacity (AEC) was found to be 2.1 to 2.4mmol/g dry microspheres. Five cell lines were cultured in static mode with the KGM microcarriers, including Vero, CHO-K1, MDCK, Wish and L929 cells. These cells adhered well and grew to high cell density comparable with or even better than those did on Cytodex 1. A further comparison was made with Vero cell culture in spinner mode. It was found that Vero cells achieved more than 2×106 cells/ml, and showed faster cell adhesion and higher specific growth rate on the KGM microcarriers than on Cytodex 1. In 5L bioreactor perfusion culture, Vero cells grew above 7.0×106 cells/ml and the rabies virus titer was about 7.7 lgLD50/ml, compared to Cytodex 1 in the same culture condition. The results suggest that the new type of microcarrier could be a promising candidate for various cell cultures. © 2014 Elsevier B.V.


Sun Y.,CAS Shanghai Institutes for Biological Sciences | Bian C.,CAS Shanghai Institutes for Biological Sciences | Xu K.,CAS Institut Pasteur of Shanghai | Hu W.,CAS Institut Pasteur of Shanghai | And 19 more authors.
PLoS ONE | Year: 2010

Background: The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. Methodology/Principal Findings: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 mg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1:40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer, <:40, Group 2). The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21) than that in Group 2 (geometric mean titer: 70 on Day 21). Conclusions/Significance: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a stronger pre-existing seasonal influenza antibody response may have a relatively higher potential for developing a stronger humoral immune response after vaccination with the 2009 A/ H1N1 pandemic influenza vaccine. © 2010 Sun et al.

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