Safety and immunogenicity of H5N1 influenza vaccine based on baculovirus surface display system of Bombyx mori.
Avian influenza virus (H5N1) has caused serious infections in human beings. This virus has the potential to emerge as a pandemic threat in humans. Effective vaccines against H5N1 virus are needed. A recombinant Bombyx mori baculovirus, Bmg64HA, was constructed for the expression of HA protein of H5N1 influenza virus displaying on the viral envelope surface. The HA protein accounted for approximately 3% of the total viral proteins in silkworm pupae infected with the recombinant virus. Using a series of separation and purification methods, pure Bmgp64HA virus was isolated from these silkworm pupae bioreactors. Aluminum hydroxide adjuvant was used for an H5N1 influenza vaccine. Immunization with this vaccine at doses of 2 mg/kg and 0.67 mg/kg was carried out to induce the production of neutralizing antibodies, which protected monkeys against influenza virus infection. At these doses, the vaccine induced 1:40 antibody titers in 50% and 67% of the monkeys, respectively. The results of safety evaluation indicated that the vaccine did not cause any toxicity at the dosage as large as 3.2 mg/kg in cynomolgus monkeys and 1.6 mg/kg in mice. The results of dose safety evaluation of vaccine indicated that the safe dose of the vaccine were higher than 0.375 mg/kg in rats and 3.2 mg/kg in cynomolgus monkeys. Our work showed the vaccine may be a candidate for a highly effective, cheap, and safe influenza vaccine for use in humans.
Jin
Rongzhong
R
College of Life Sciences, Zhejiang University, Hangzhou, China.
Lv
Zhengbing
Z
Chen
Qin
Q
Quan
Yanping
Y
Zhang
Haihua
H
Li
Si
S
Chen
Guogang
G
Zheng
Qingliang
Q
Jin
Lairong
L
Wu
Xiangfu
X
Chen
Jianguo
J
Zhang
Yaozhou
Y
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016367:Baculoviridae / Q000378:metabolism*; D012831:Bombyx / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007109:Immunity; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D051379:Mice; D008970:Molecular Weight; D009500:Neutralization Tests; D011679:Pupa / Q000821:virology; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017186:Titrimetry; D014611:Vaccination
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins