Effect of AcHERV-GmCSF as an Influenza Virus Vaccine Adjuvant

Abstract

IntroductionThe first identification of swine-originated influenza A/CA/04/2009 (pH1N1) as the cause of an outbreak of human influenza accelerated efforts to develop vaccines to prevent and control influenza viruses. The current norm in many countries is to prepare influenza vaccines using cell-based or egg-based killed vaccines, but it is difficult to elicit a sufficient immune response using this approach. To improve immune responses, researchers have examined the use of cytokines as vaccine adjuvants, and extensively investigated their functions as chemoattractants of immune cells and boosters of vaccine-mediated protection. Here, we evaluated the effect of Granulocyte-macrophage Colony-Stimulating Factor (GmCSF) as an influenza vaccine adjuvant in BALB/c mice.Method and ResultsFemale BALB/c mice were immunized with killed vaccine together with a murine GmCSF gene delivered by human endogenous retrovirus (HERV) envelope coated baculovirus (1×107 FFU AcHERV-GmCSF, i.m.) and were compared with mice immunized with the killed vaccine alone. On day 14, immunized mice were challenged with 10 median lethal dose of mouse adapted pH1N1 virus. The vaccination together with GmCSF treatment exerted a strong adjuvant effect on humoral and cellular immune responses. In addition, the vaccinated mice together with GmCSF were fully protected against infection by the lethal influenza pH1N1 virus.ConclusionThus, these results indicate that AcHERV-GmCSF is an effective molecular adjuvant that augments immune responses against influenza virus.

Porcine endogenous retrovirus envelope coated baculoviral DNA vaccine against porcine reproductive and respiratory syndrome virus

“…Previously, we applied the HPV and influenza vaccine using the AcHERV system. 5,6 We confirmed that the immune response continues to increase after 3 times vaccination with AcHERV system. The increase in immune responses to HPV or influenza suggests that vaccination using the AcHERV system has no problems in gene delivery because of the low immune response to endogenous retroviral envelope proteins in mice.…”

“…Previously, we reported the immunization efficacy of influenza DNA vaccines based on a HERV-coated baculoviral DNA vaccine system for human use. 5,21 In this study, we successfully constructed a PERVenveloped baculovirus delivery system for porcine use. Compare to full length of PERV env, signal sequence and transmembrane modified PERV env showed more efficient delivery.…”

“…Previously, we reported that a non-replicable baculovirus vector containing antigen-encoding DNA serves as an effective delivery system for human-infecting viral DNA antigens and improves exogenous DNA vaccine delivery into cells via receptors recognizing the human endogenous retrovirus (HERV) envelope on baculovirus. 5,6 Here, we constructed a recombinant vector with a surface coating of the PERV envelope instead of HERV, to apply the endogenous retrovirus-modified baculovirus vector for porcine DNA vaccination.…”

Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1

“…In brief, blood samples were collected from mice and sera were obtained. Ninety-six well plates were coated overnight with 8 hemagglutination units (HAU) of inactivated pH1N1 using standard methods, as previously described [ 30 , 31 ]. The absorbance at 450 nm (A450) was measured using an ELISA plate reader (Bio-Rad, Hercules, CA, USA).…”

Human endogenous retroviruses in viral disease and therapy

“…Choi et al reported that female mice immunized with an inactivated influenza vaccine together with a murine granulocyte-macrophage colony-stimulating factor (GmCSF) gene delivered by the AcHERV system showed stronger humoural and cellular immune responses than mice immunized with the inactivated vaccine alone.Influenza-GmCSF-vaccinated mice were fully protected from lethal influenza virus challenge. 77 These findings showed that HERVs exhibit multiple functions in vaccine design. Recently, Segel et al identified one LTR retrotransposon homolog, paternally expressed gene 10 (PEG10) that preferentially bound and facilitated vesicular secretion of messenger RNA (mRNA).…”