Heat shock protein 70 fused to or complexed with Hantavirus nucleocapsid protein significantly enhances specific humoral and cellular immune responses in C57BL/6 mice

Summary Heat shock proteins (HSPs) are known to act as an effective molecular adjuvant to enhance the induction of antigen peptide-specific cellular immunity, when coupled with the antigen or peptide. Hantaan virus (HTNV) nucleocapsid protein (NP) is relatively conserved among hantaviruses and highl...

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Bibliographic Details
Published in:Vaccine 2008-06, Vol.26 (25), p.3175-3187
Main Authors: Li, Jing, Li, Kai Nan, Gao, Juan, Cui, Ji Hong, Liu, Yan Fang, Yang, Shou Jing
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Antibodies, Viral - blood
Antibody Formation - drug effects
Antibody Formation - immunology
Antigens
Applied microbiology
Biological and medical sciences
Capsid Proteins - administration & dosage
Capsid Proteins - chemistry
Capsid Proteins - immunology
Cytotoxic T lymphocyte
Deoxyribonucleic acid
DNA
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Hantaan virus
Hantavirus
Hantavirus - chemistry
Heat-shock protein 70
HSP70 Heat-Shock Proteins - administration & dosage
HSP70 Heat-Shock Proteins - chemistry
HSP70 Heat-Shock Proteins - immunology
Humoral immunity
Immune system
Immunity, Cellular - drug effects
Immunity, Cellular - immunology
Infections
Lymphocytes
Mice
Mice, Inbred C57BL
Microbiology
Miscellaneous
Mortality
Nucleocapsid protein
Peptides
Protein vaccine
Proteins
Recombinant Fusion Proteins - immunology
RNA polymerase
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Viral Core Proteins - administration & dosage
Viral Core Proteins - chemistry
Viral Core Proteins - immunology
Viral Vaccines - administration & dosage
Viral Vaccines - immunology
Virology
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Summary:Summary Heat shock proteins (HSPs) are known to act as an effective molecular adjuvant to enhance the induction of antigen peptide-specific cellular immunity, when coupled with the antigen or peptide. Hantaan virus (HTNV) nucleocapsid protein (NP) is relatively conserved among hantaviruses and highly immunogenic in both animals and humans. To analyze the influence of HSP70 on NP vaccine potency, and evaluate the possibility of developing a novel effective vaccine against hantaviruses, we constructed prokaryotic expression plasmids, and expressed three recombinant proteins, namely, HTNV NP, HSP70 and HSP70 − NP fusion protein. As an alternative to fusion protein, we also generated HSP70 and HTNV NP complexes (HSP70 + NP) in vitro . C57BL/6 mice were immunized with those recombinant proteins, the humoral and cellular responses elicited against NP were measured by ELISA, fluorescence flow cytometry, cytotoxicity assays, and IFN-γ ELISPOT assay. We found that immunization of mice with HSP70 − NP fusion protein, or HSP70 + NP complexes elicited significantly higher NP-specific antibody titers, frequencies of IFN-γ-producing cells and cytotoxic T lymphocyte (CTL) activities in vivo than conventional HTNV NP vaccination. Antibody isotype analysis showed that the antibody response was characterized by a higher HTNV NP-specific titer of IgG2a than IgG1 antibodies, resulting in a significant higher IgG2a/IgG1 ratio. By comparison, HSP70 − NP fusion protein is significantly superior to HSP70 + NP complexes in enhancement of NP antigenicity. These results indicated that HSP70, when fused to or complexed with HTNV NP, greatly enhance NP vaccine potency by preferential induction of a predominant Th1 immune response in a NP-specific, HSP70-dependent manner.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.02.066