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Characterization of the immune responses elicited by baculovirus-based vector vaccines against influenza virus hemagglutinin.

ABSTRACT: AIM: To compare the specific immune responses elicited by different baculovirus vectors in immunized mice. METHODS: We constructed and characterized two recombinant baculoviruses carrying the expression cassette for the H5N1 influenza virus hemagglutinin (HA) gene driven by either an insect cell promoter (vAc-HA) or a dual-promoter active both in insect and mammalian cells (vAc-HA-DUAL). Virus without the HA gene (vAc-EGFP) was used as a control. These viruses were used to immunize mice subcutaneously and intraperitoneally. The production of total and specific antibodies was determined by ELISA and competitive ELISA. Cytokine production by the spleen cells of immunized mice was studied using the ELISPOT assay. RESULTS: Both the vAc-HA and vAc-HA-DUAL vectors expressed HA proteins in insect Sf9 cells, and HA antigen was present in progeny virions. The vAc-HA-DUAL vector also mediated HA expression in virus-transduced mammalian cell lines (BHK and A547). Both vAc-HA and vAc-HA-DUAL exhibited higher transduction efficiencies than vAc-EGFP in mammalian cells, as shown by the expression of the reporter gene egfp. Additionally, both vAc-HA and vAc-HA-DUAL induced high levels of HA-specific antibody production in immunized mice; vAc-HA-DUAL was more efficient in inducing IFN-? and IL-2 upon stimulation with specific antigen, whereas vAc-HA was more efficient in inducing IL-4 and IL-6. CONCLUSION: Baculovirus vectors elicited efficient, specific immune responses in immunized mice. The vector displaying the HA antigen on the virion surface (vAc-HA) elicited a Th2-biased immune response, whereas the vector displaying HA and mediating HA expression in the cell (vAc-HA-DUAL) elicited a Th1-biased immune response.

SUBMITTER: Hu ZP

PROVIDER: S-EPMC4010374 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Characterization of the immune responses elicited by baculovirus-based vector vaccines against influenza virus hemagglutinin.

Hu Zhi-peng ZP Yin Juan J Zhang Yuan-yuan YY Jia Shu-ya SY Chen Zuo-jia ZJ Zhong Jiang J

Acta pharmacologica Sinica 20120507 6

<h4>Aim</h4>To compare the specific immune responses elicited by different baculovirus vectors in immunized mice.<h4>Methods</h4>We constructed and characterized two recombinant baculoviruses carrying the expression cassette for the H5N1 influenza virus hemagglutinin (HA) gene driven by either an insect cell promoter (vAc-HA) or a dual-promoter active both in insect and mammalian cells (vAc-HA-DUAL). Virus without the HA gene (vAc-EGFP) was used as a control. These viruses were used to immunize ...[more]

PMID: 22562016

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Project description:We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination (T0), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination (T1), and 3 to 4 weeks after the second vaccination (T2). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T1, the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T1 and T2. The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T2. The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T2. The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL-1) and 12.0 IU mL-1, respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.

Dataset Information

Characterization of the immune responses elicited by baculovirus-based vector vaccines against influenza virus hemagglutinin.

Publications

Characterization of the immune responses elicited by baculovirus-based vector vaccines against influenza virus hemagglutinin.

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