Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology

Abstract

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax TM , a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax TM . Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which Advax TM adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (»10EC3pfu/g) in mice administered vaccine with either Advax TM adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with Advax TM was similar to Imject Alum. Overall, RSV vaccine formulated with Advax TM had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared to unvaccinated mice.

Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice

“…Pathological change and viral load were inconsistent in lung tissue for PBS and RSV-F alone groups, where pulmonary pathology lagged behind virus clearance. A similar phenomenon is reported in other studies (46,47). Further study is needed to check the time course of virus clearance and lung inflammatory response more frequently.…”

Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles

“…31 Mice vaccinated with Vac-G or FI-RSV and treated with a natural killer T cell activating adjuvant (a-GalCer) or live RSV vaccine plus delta-inulin adjuvant did not diminish lung histopathology after RSV challenge. 37,38 Interestingly, addition of F VLP to F protein vaccination was found to improve protective efficacy and to suppress F protein vaccine-enhanced lung histopathology in infant age mice (data not shown). It is important to determine whether F VLP with Th2 bias immune inducing adjuvant will result in vaccine enhanced disease.…”

Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection

“…9 Advax is an adjuvant derived from delta inulin, a polysaccharide found in the roots of plants of the Compositae family. 10,11 Advax adjuvant has shown high levels of efficacy in vaccines against respiratory syncytial virus, 11 West Nile virus and Japanese encephalitis virus, 12,13 influenza, [14][15][16] severe acute respiratory syndrome coronavirus, 17 Listeria, 18 onchocercosis 19 and anthrax, 20 amongst others, consistent with its having broad efficacy across viral, bacterial and parasitic vaccines. An advantage of delta inulin adjuvant is that it enhances both Th1 and Th2 T cell responses.…”