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Lu J.,Jilin University | Sun T.,Jilin University | Wang D.,Jilin University | Dong Y.,Jilin University | And 11 more authors.
Immunological Investigations | Year: 2015

Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Due to drawbacks of the current polysaccharide-based vaccine, the most promising way to generate an improved vaccine may be to utilize protection-eliciting pneumococcal proteins. Pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA) are two vaccine candidates which have been evaluated against S. pneumoniae infection in animal models or human clinical trials with encouraging results. In this study, the efficacy of the fusion protein PsaA-PspA, which includes PsaA part and PspA part, in inducing immunoprotective effects against fatal pneumococcal challenge was evaluated in an animal model. PspA part of PsaA-PspA fusion protein contains both family1 N-terminal region and family 2 N-terminal clade-defining region of PspA. Immunization with the PsaA-PspA fusion protein induced high levels of antibodies against both PsaA and PspA, which could bind to intact S. pneumoniae strains bearing different PspAs. Ex vivo stimulation of splenocytes from mice immunized with PsaA-PspA induced IL-17A secretion. Mice immunized with PsaA-PspA showed reduced S. pneumoniae levels in the blood and lungs compared with the PBS group after intranasal infection. Finally, mice immunized with PsaA-PspA fusion proteins were protected against fatal challenge with pneumococcal strains expressing different PspAs regardless of the challenge route. These results support the PsaA-PspA fusion protein as a promising vaccine strategy, as demonstrated by its ability to enhance the immune response and stimulate production of high titer antibodies against S. pneumoniae strains bearing heterologous PspAs, as well as confer protection against fatal challenge with PspA family 1 and family 2 strains. © 2015 Informa Healthcare USA, Inc. Source


Zhao Z.-Y.,Changchun BCHT Biotechnology Company
Chinese Journal of Biologicals | Year: 2012

Objective: To observe the adverse reaction and immune response in populations at various ages after immunization with rabies vaccine for human use. Methods: A total of 627 healthy subjects without history of injury by dogs or rabies vaccination were selected and divided into five age groups. Venous blood samples were collected before and 14 and 45 d after the first vaccination respectively, from which sera were separated and determined for antibody titer against rabies virus by rapid fluorescence focus inhibition test (RFFIT), and GMT was calculated. Of the subjects, 225 were selected and observed for adverse reactions. Results: The total local and systemic adverse reaction rates in 225 subjects were 5.15% and 4.42% respectively. All the reactions were mild or moderate, while no severe or serious adverse reactions were reported. All the serum samples before vaccination were negative for antibody (GMT ≤ 0.2 IU/ml). All the antibody positive rates in populations of various age groups were 100% 14 d after the first vaccination. However, the GMTs of antibodies showed significant difference in various groups (P < 0.05), which were high in the populations at ages of 4 ∼ 6 and 7 ∼ 16 years (9.42 and 9.01 IU/ml respectively, P > 0.05) and low in those at 1 ∼3 and not less than 41 years (6.11 and 6.35 IU/ml respectively, P > 0.05). All the antibody positive rates in various groups were still 100% 45 d after the first vaccination, while the GMTs were 14.8 ∼ 16.40 IU/ml, which showed no significant difference (P > 0.05). Conclusion: Mild adverse reactions and good immune responses were induced by rabies vaccination in populations at various ages. However, the antibody productions in infants at age of less than 3 years and in the aged were prone to be delayed. It is suggested that the dosages of rabies vaccine for the first and second vaccinations in infants and the aged should be added properly so as to increase the serum antibody positive rate and the success rate of immunization. Source


Sun S.,Jilin University | Jiang L.,Jilin University | Liang Z.,National Institutes for Food and Drug Control | Mao Q.,National Institutes for Food and Drug Control | And 15 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

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 EV71+CVA16 virus (iEV71+iCVA16) and EV71+CVA16 VLPs (vEV71+vCVA16). 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 LD50 of EV71 and 50 LD50 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. © 2014 Taylor & Francis Group, LLC. Source


Zang Y.,Jilin University | Du D.,Jilin University | Li N.,Jilin University | Su W.,Jilin University | And 6 more authors.
Vaccine | Year: 2015

Despite significant efforts directed toward research on HIV-1 vaccines, a truly effective immunogen has not been achieved. However, the broadly neutralizing antibodies (BnAbs) 2F5 and 4E10, targeting the highly conserved membrane proximal external region (MPER) of HIV-1, are two promising tools for vaccine development. Here we engrafted the MPER into the linker domain between the trimeric core structure and the transmembrane domain of influenza A virus HA2 to investigate the potential of such chimeric viruses to elicit HIV-1 neutralizing antibodies. In the context of proliferating attenuated influenza A viruses, these HIV-1 neutralizing antibody epitopes could be continuously expressed and mimicked their native conformation to induce humoral immune responses. While MPER-specific antibodies could be detected in serum of guinea pigs vaccinated with the chimeric viruses, they exhibited only weakly neutralizing activities. These antisera from vaccinated animals neutralized viruses of clades B and BC (tier 1), but not of clades AE (tier 1) and C (tier 2). These results suggest that influenza A virus can be used as a vehicle for displaying MPER and inducing BnAbs, but it provides limited protection against HIV-1 infection. In the future development of HIV-1 vaccines by rational design, a more effective live virus vector or multiple antigens should be chosen to facilitate the process of neutralizing antibody maturation. © 2015 Elsevier Ltd. Source


Li N.,Jilin University | Qi Y.,Jilin University | Zhang F.Y.,Changchun BCHT Biotechnology Company | Yu X.H.,Jilin University | And 4 more authors.
Acta Virologica | Year: 2011

Human influenza viruses are major concern as the leading cause of global pandemics. In infecting cells, they preferentially bind to sialyloligosaccharides containing terminal N-acetyl sialic acid linked to galactose by an α-2,6-linkage (NeuAcα2,6Gal). The amount of NeuAcα2,6Gal in Vero cells, which are predominantly used for production of influenza vaccines over the past 30 years, may not be as high as that in epithelial cells of human respiratory tract, what leads to the suboptimal virus growth in Vero cells. In this study, we stably transfected Vero cells with cDNA of human α-2,6-sialyltransferase (SIAT1), an enzyme catalyzing α-2,6-sialylation of galactose on glycoproteins. Overexpression of SIAT1 in the transfected Vero cells (Vero-SIAT1 cells) was confirmed by Western blot analysis and immunofluorescence microscopy. Vero-SIAT1 cells expressed 7 times higher amounts of NeuAcalpha;α2,6Gal, but 3 times lower amounts of NeuAcα2,3Gal as compared to parental Vero cells. Furthermore, the influenza viruses A (H1N1 and H3N2) and B grew in Vero-SIAT1 cells to the higher titers than in Vero cells. Taken together, these results imply that Vero-SIAT1 cells are useful not only for the propagation of human influenza viruses, but also for the preparation of influenza vaccines. Source

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