Abstract
Baculovirus is a promising vaccine deliver vector due to its biosafety profiles, gene transfer efficiency, ability to display small foreign antigens on its surface, strong adjuvant activities, etc. A dual vector for peptide antigens and a DNA vaccine delivery was constructed. In this vector, a tetrameric glycoprotein neuraminidase (NA) from influenza A virus (H5N1) serves as a baculovirus surface protein to improve baculovirus transduction efficiency and a partner for displaying the target peptide antigen. Nucleotides encoding target peptides could be fused to a full length NA gene, at the lower part of its head structure, integrated into Autographa californica multinucleopolyhedrovirus genome and expressed under the control of a White Spot Syndrome Virus IE-1 shuttle promoter. Angiotensin II (AngII) peptides, a potent vasoconstrictor that causes high blood pressure, was our target antigen. The recombinant NA-AngII pseudotyped baculovirus had the AngII peptides fused to the NA and displayed on its surface. In vitro studies revealed that this recombinant baculovirus successfully delivered AngII peptides, as DNA vaccine, into human HEK293A cells. A single subcutaneous injection of the recombinant NA-AngII pseudotyped baculovirus into moderately high blood pressure rats at 4 × 109 pfu/rat, stimulated anti-AngII antibody production and their systolic blood pressure (SBP) levels were found to have decreased. In addition, a single intranasal immunization at 8 × 108 pfu/rat, raised anti-AngII antibodies in a rat and its SBP was also reduced. The recombinant neuraminidase pseudotyped baculovirus is a potential vector for AngII peptide antigen and DNA vaccine for subcutaneous or intranasal immunization for treatment of hypertension.
Highlights
The insect baculovirus Autographa californica multinucleopolyhedrovirus (AcMNPV) is an enveloped virus containing a circular double-stranded DNA genome with ease of genetic manipulation and high titer production (Airenne et al 2013)
Recombinant neuraminidase pseudotyped baculovirus as Angiotensin II (AngII) peptide presenting vector AcMNPV baculovirus was pseudotyped with influenza A (H5N1) neuraminidase fused with an AngII peptide
Western blot analysis of the recombinant baculovirus revealed a protein being recognized by both anti-NA polyclonal antibody and anti-AngII peptide monoclonal antibody with a molecular weight of approximately 55 kDa which corresponded to the neuraminidase-AngII fusion protein (Fig. 2b)
Summary
The insect baculovirus Autographa californica multinucleopolyhedrovirus (AcMNPV) is an enveloped virus containing a circular double-stranded DNA genome with ease of genetic manipulation and high titer production (Airenne et al 2013). Other foreign transmembrane proteins such as influenza virus neuraminidase (NA) and vesicular stomatitis virus G protein (VSV-G) were employed to display peptides on the baculovirus lateral regions (Chapple and Jones 2002; Borg et al 2004). Baculovirus is known for its adjuvant properties by enhancing humoral and cellular immune responses against target antigens. Baculovirus activates innate immune responses by inducing type I and II IFNs (Abe et al 2005; HervasStubbs et al 2007; Suzuki et al 2010; Heinmäki et al 2017) and has ability to stimulate mucosal immune system by a needle-free, painless and stress free administration. Intranasal administrations with the recombinant hemagglutinin (HA) baculovirus were reported to protect immunized mice from a lethal influenza infection (Abe et al 2003). Oral administration of recombinant baculovirus expressing H5N1 vaccine induced high level of mucosal, and systemic immune responses (Prabakaran et al 2010)
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