Comparative Safety and Efficacy Profile of a Novel Oil in Water Vaccine Adjuvant Comprising Vitamins A and E and a Catechin in Protective Anti-Influenza Immunity

Abstract

Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA) mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS), based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus. Vaccinations of inbred Brag Albino strain c (BALB/c) mice, with HA mixed with NIDS compared to other adjuvants, i.e., a squalene oil in water emulsion (Sq. oil), and the Toll Like Receptor 3 (TLR3) agonist Poly (I:C), induced significantly lower select innate pro-inflammatory responses in serum, but induced significantly higher adaptive antibody and splenic T Helper 1 (TH1) or TH2, but not TH17, responses. Vaccinations with NIDS protected against infection, as measured by clinical scores, lung viral loads, and serum hemagglutination inhibition titers. The NIDS exhibited a strong dose sparing effect and the adjuvant action of NIDS was intact in the outbred CD1 mice. Importantly, vaccinations with the Sq. oil, but not NIDS, induced a significantly higher Serum Amyloid P component, an acute phase reactant secreted by hepatocytes, and total serum IgE. Thus, the NIDS may be used as a clinically safer and more efficacious vaccine adjuvant against influenza, and potentially other infectious diseases.

Safety and Efficacy of the Bordetella bronchiseptica Vaccine Combined with a Vegetable Oil Adjuvant and Multi-Omics Analysis of Its Potential Role in the Protective Response of Rabbits

“…E515 is a novel vegetable oil adjuvant that consists of soybean oil, vitamin E (VE), and ginseng saponins (GS). Compared to mineral oil and Alum, vegetable oil-derived E515 is much safer, which conforms to the standard of the Chinese Pharmacopoeia; VE is a nutritional factor, and GS is derived from a tonic herb [ 18 , 19 ]. Our previous studies verified that E515 significantly enhances the humoral and cellular immune responses induced by foot-and-mouth disease (FMD) vaccines in mice and Hu sheep [ 20 , 21 ].…”

Editorial: Induction and Maintenance of Long-Term Immunological Memory Following Infection or Vaccination

“…The issue of memory induction following vaccination is linked to vaccine adjuvants and delivery systems, and their nature as replicating, metabolically alive but non-replicating, or non-living and non-replicating (such as TLR agonists, Alum, etc.) The commonly unwritten rule is that vaccine adjuvants and delivery systems must induce pro-inflammatory innate responses in order to induce acute and memory responses, although this view has recently been challenged by the introduction of a vaccine adjuvant that induced strong adaptive B and T cell responses in the absence of strong innate immune responses (2, 3).…”