Protective effect of a RSV subunit vaccine candidate G1F/M2 was enhanced by a HSP70-Like protein in mice.
Respiratory syncytial virus (RSV) is a major respiratory pathogen in newborns. Neonate vaccine should induce strong protective immunity. We have engineered a subunit vaccine candidate G1F/M2. A major problem in developing subunit vaccines is their limited immunogenicity. Aluminium adjuvants with a long history of use with routine childhood vaccines have some limitations, especially inability to elicit CTL response. There is a need for alternative adjuvants. Heat shock proteins (HSPs) are characterized as potent immunoadjuvants. In this study, HSP70-like protein 1 (HSP70L1) gene was cloned. The recombinant protein HSP70L1 was expressed in E. coli, purified and renaturated. We evaluated the potential of HSP70L1 used as the adjuvant of G1F/M2. G1F/M2 was chemically cross-linked with HSP70L1 (HSP-G1F/M2). HSP70L1 enhanced significantly the immunogenicity and protective effect of G1F/M2. HSP-G1F/M2 induced significant higher levels of antibodies, neutralizing antibodies and CTL activity than unadjuvanted G1F/M2. The antibody titers induced by HSP-G1F/M2 were similar to that by G1F/M2+Alum. RSV-specific CTL activity induced by HSP-G1F/M2 was stronger than that by G1F/M2+Alum. Interestingly, the protective effect of HSP-G1F/M2 against RSV was significantly stronger than that of G1F/M2+Alum. The results suggest that HSP70L1 is a potent adjuvant of G1F/M2.
Zeng
Ruihong
R
Department of Immunology, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang, Hebei province 050017, China. Electronic address: zengruihong@yahoo.com.cn.
Zhang
Zhenya
Z
The First Affiliated Hospital, Tsinghua University, Beijing 100016, China.
Mei
Xingguo
X
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Gong
Wei
W
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Wei
Lin
L
Department of Immunology, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang, Hebei province 050017, China.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D018840:HSP70 Heat-Shock Proteins; C483693:Hspa14 protein, human; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit