Protection, systemic IFNγ, and antibody responses induced by an ISCOM-based vaccine against a recent equine influenza virus in its natural host

Abstract

-In the horse, conventional inactivated or subunit vaccines against equine influenza virus (EIV) induce a short-lived antibody-based immunity to infection. Alternative strategies of vaccination have been subsequently developed to mimic the long-term protection induced by natural infection with the virus. One of these approaches is the use of immune-stimulating complex (ISCOM)-based vaccines. ISCOM vaccines induce a strong antibody response and protection against influenza in horses, humans, and a mouse model. Cell-mediated immunity (CMI) has been demonstrated in humans and mice after ISCOM vaccination, but rarely investigated in the horse. The aim of this study was to evaluate EIV-specific immune responses after intra-muscular vaccination with an ISCOM-EIV vaccine (EQUIP F) containing both equine influenza H7N7 (A/eq/Newmarket/77) and H3N8 (A/eq/Borlänge/91 and A/eq/Kentucky/98) strains. The antibody response was measured by single radial haemolysis (SRH) assay using different H3N8 EIV strains. Stimulation of type-1 immunity was evaluated with a recently developed method that measures EIV-specific IFN synthesis by peripheral blood lymphocytes (PBL). The protective efficacy of this ISCOM-based vaccine against challenge infection with a recent equine influenza (H3N8; A/eq/South Africa/4/03) strain was also evaluated. Vaccinated ponies developed elevated levels of EIV-specific SRH antibody and increased percentage of EIV-specific IFN + PBL, whereas these responses were only detected after challenge infection in unvaccinated control ponies. Vaccinates showed minimal signs of disease and did not shed virus when challenged shortly after the second immunisation. In conclusion, evidence of type-1 immunity induced by an ISCOM-based vaccine is described for the first time in horses. equine influenza virus / vaccine / ISCOM / equine IFN gamma / immunity

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

“…[31][32][33][34][35][36] Immune-stimulating complexes (ISCOMs), composed of saponins, cholesterol, and phospholipids, are a distinct class of adjuvant that act through both inflammatory and IFN pathways to enhance Ag uptake by DCs. [37][38][39][40][41] Recent studies have used systems serology analyses to qualitatively assess antibody responses based on Fc-mediated effector functions, [42][43][44][45][46][47] which have been found to play a role in protection against simian immunodeficiency virus (SIV) 48 and HIV. 4 To assess the mechanisms by which adjuvants and vaccines mediate such effector functions, transcriptional profiling has been used in mouse models, [49][50][51][52] as well as in humans to define biomarkers to predict protection.…”

ISCOM-based equine influenza vaccine: Duration of immunity and randomised clinical trials to assess an accelerated schedule of immunisation and efficacy

“…Viruses were all grown in embryonated hen's eggs, purified and titrated as described previously [9]. The EIV strain A/eq/Richmond/1/07 (passage 4 in eggs) was used for experimental infection in the context of the efficacy study (Study 3) and was titrated in embryonated hens' eggs prior to challenge (day 58).…”

“…Equip FT is the same vaccine complemented with the TT antigen. The Equip F ISCOM-based EI vaccine has been shown to stimulate both humoral and CMI [9] and to provide significant protection when tested at the peak of immunity (2 weeks after the second immunisation) against the representative outbreak EIV strains A/eq/South Africa/4/03 [9] and A/eq/Sydney/288-8/07 [10] of the Florida clade 1 sublineage [11][12][13]. This EI vaccine contains H3N8 EIV isolates (A/eq/Borlange/91 and A/eq/Kentucky/98; H3N8; European and American lineages, respectively), which present antigenic and genetic differences from the current Florida clade 2 EIV strains circulating in Europe or the Florida clade 1 isolates predominantly circulating in the US [12,14,15].…”

“…The immune response stimulated after only one immunisation (V1) is usually transient and of low intensity with most EI vaccines [9,16]. While vaccinated horses may present reduced clinical signs of disease and virus shedding after a single immunisation, as illustrated in the 2007 Australian outbreak [17], they usually remain susceptible to EIV infection until several days after the second immunisation (V2) of the primary course.…”

Equine Herpes Virus-1: Virus, Immunity and Vaccines

“…8). In other species, ISCOM™ or Iscomatrix™-based vaccines have shown successful protection against numerous pathogens [125] and are successfully used against EIV in the horse [126][127][128]. ISCOMs and Iscomatrix™ are not fusogenic but can associate with intracellular lipid membranes in the cytoplasm and vesicular compartments after up-take by APC [129].…”