Abstract
Despite the advantages of DNA vaccines, overcoming their lower efficacy relative to that of conventional vaccines remains a challenge. Here, we constructed a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus-based HA vaccine against swine influenza A/California/04/2009(H1N1) hemagglutin (HA) (AcHERV-sH1N1-HA) as an alternative to conventional vaccines and evaluated its efficacy in two strains of mice, BALB/c and C57BL/6. A commercially available, killed virus vaccine was used as a positive control. Mice were intramuscularly administered AcHERV-sH1N1-HA or the commercial vaccine and subsequently given two booster injections. Compared with the commercial vaccine, AcHERV-sH1N1-HA induced significantly higher levels of cellular immune responses in both BALB/c and C57BL/6 mice. Unlike cellular immune responses, humoral immune responses depended on the strain of mice. Following immunization with AcHERV-sH1N1-HA, C57BL/6 mice showed HA-specific IgG titers 10- to 100-fold lower than those of BALB/c mice. In line with the different levels of humoral immune responses, the survival of immunized mice after intranasal challenge with sH1N1 virus (A/California/04/2009) depended on the strain. After challenge with 10-times the median lethal dose (MLD50) of sH1N1 virus, 100% of BALB/c mice immunized with the commercial vaccine or AcHERV-sH1N1-HA survived. In contrast, C57BL/6 mice immunized with AcHERV-sH1N1-HA or the commercial vaccine showed 60% and 70% survival respectively, after challenge with sH1N1 virus. In all mice, virus titers and results of histological analyses of lung tissues were consistent with the survival data. Our results indicate the importance of humoral immune response as a major defense system against influenza viral infection. Moreover, the complete survival of BALB/c mice immunized with AcHERV-sH1N1-HA after challenge with sH1N1 virus suggests the potential of baculoviral vector-based vaccines to achieve an efficacy comparable to that of killed virus vaccines.
Highlights
Influenza A viruses of the Orthomyxoviridae family, which have a genome composed of eight segments of negative single-strand RNA, are the causative agents of influenza [1,2,3].After infection, two glycoproteins of the influenza virus membrane—hemagglutin (HA) and neuraminidase (NA)— emerge in the body during replication cycles in response to host immunological pressure, resulting in new epidemic strains every 1 to 2 years [4]
The construction of recombinant baculovirus AcHERV-swine influenza H1N1 (sH1N1)-HA was confirmed by amplification of human endogenous retrovirus (HERV) and HA genes by polymerase chain reaction (PCR), which showed that the HERV envelope gene and sH1N1 HA gene were correctly inserted in the AcHERV-sH1N1-HA construct (Figure 2A)
Unlike mice immunized with killed virus vaccines, mice treated with the AcHERV-sH1N1-HA vaccine showed 410 ± 45 and 423±47 IFN-γ spots per 2 × 106 splenocytes for C57BL/6 and BALB/C mice, respectively (Figure 3)
Summary
Influenza A viruses of the Orthomyxoviridae family, which have a genome composed of eight segments of negative single-strand RNA, are the causative agents of influenza [1,2,3].After infection, two glycoproteins of the influenza virus membrane—hemagglutin (HA) and neuraminidase (NA)— emerge in the body during replication cycles in response to host immunological pressure, resulting in new epidemic strains every 1 to 2 years [4]. Influenza A viruses of the Orthomyxoviridae family, which have a genome composed of eight segments of negative single-strand RNA, are the causative agents of influenza [1,2,3]. There are currently 17 known HA subtypes (H1–17) and nine known NA subtypes (N1–9) with a number of possible combinations between HA and NA (N1-N9) [5,6]. In April 2009, an outbreak of influenza in North America was found to be caused by the swine-origin influenza virus A/ California/04/2009(H1N1). The virus has been rapidly spread by people and by August 1, 2010, more than 214 countries and overseas territories worldwide had reported laboratoryconfirmed cases of pandemic influenza H1N1 2009, including over 18,449 deaths [7]. H1N1 influenza has moved into the post-pandemic period and circulates as a seasonal virus
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