Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

So-Yon Lim,Swapan K Ghosh,Adam Bauermeister,Richard A Kjonaas

doi:10.1186/1476-8518-4-5

So-Yon Lim, Swapan K Ghosh + Show 2 more

Open Access

https://doi.org/10.1186/1476-8518-4-5

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Abstract

BackgroundAdjuvants are known to significantly enhance vaccine efficacy. However, commercial adjuvants often have limited use because of toxicity in humans. The objective of this study was to determine the comparative effectiveness of a diterpene alcohol, phytol and its hydrogenated derivative PHIS-01, relative to incomplete Freund's adjuvant (IFA), a commonly used adjuvant in augmenting protective immunity in mice against E. coli and S. aureus, and in terms of inflammatory cytokines.MethodsVaccines, consisting of heat-attenuated E. coli or S. aureus and either of the two phytol-based adjuvants or IFA, were tested in female BALB/c mice. The vaccines were administered intraperitoneally at 10-day intervals. The efficacy of the phytol and PHIS-01, as compared to IFA, was assessed by ELISA in terms of anti-bacterial antibody and inflammatory cytokines. We also examined the ability of the vaccines to induce specific protective immunity by challenging mice with different doses of live bacteria.Results and discussionIFA, phytol, and PHIS-01 were equally efficient in evoking anti-E. coli antibody response and in providing protective immunity against live E. coli challenges. In contrast, the antibody response to S. aureus was significant when PHIS-01 was used as the adjuvant. However, in terms of the ability to induce protective immunity, phytol was most effective against S. aureus. Moreover, during challenges with live E. coli and S. aureus immune mice produced much less IL-6, the mediators of fatal septic shock syndromes.ConclusionOur results show that vaccine formulations containing phytol and PHIS-01 as adjuvants confer a robust and protective immunity against both Gram-negative and Gram-positive bacteria without inducing adverse inflammatory cytokine due to IL-6.

Highlights

Adjuvants are known to significantly enhance vaccine efficacy
Our results show that vaccine formulations containing phytol and PHIS-01 as adjuvants confer a robust and protective immunity against both Gram-negative and Gram-positive bacteria without inducing adverse inflammatory cytokine due to IL-6
Specific anti-bacterial antibody responses Sera of immunized mice collected over the course of three immunizations were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) to determine the induction and duration of antibody response

Summary

Introduction

Adjuvants are known to significantly enhance vaccine efficacy. commercial adjuvants often have limited use because of toxicity in humans. Protective immunity in vertebrates depends largely on efficient activation and subsequent interactions of cells belonging to both innate and acquired immunity. The innate component, has no memory and is first to respond with only a limited repertoire to recognize pathogen-associated molecular patterns (PAMPs), usually present in the cell wall structures of microbes [1,2,3]. Vaccines that interact with both components of the immune system have the ability to induce effective prophylaxis against a variety of infectious diseases. Most anti-microbial vaccines in current use have been designed to stimulate antibody responses, and the development of effective cellmediated immunity is important to overcome chronic infectious diseases associated with intracellular pathogens and viruses [10]. In spite of historical successes with killed or attenuated microbes as vaccines, the looming threat of new and resistant pathogens requires development of new and improved versions of vaccines

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