Abstract
Protein/subunit vaccines often require external adjuvants to induce protective immunity. Due to the safety concern of chemical adjuvants, physical adjuvants were recently explored to boost vaccination. Physical adjuvants use physical energies rather than chemicals to stimulate tissue stress and endogenous danger signal release to boost vaccination. Here we present the safety and potency of non-invasive radiofrequency treatment to boost intradermal vaccination in murine models. We show non-invasive radiofrequency can increase protein antigen-induced humoral and cellular immune responses with adjuvant effects comparable to widely used chemical adjuvants. Radiofrequency adjuvant can also safely boost pandemic 2009 H1N1 influenza vaccination with adjuvant effects comparable to MF59-like AddaVax adjuvant. We find radiofrequency adjuvant induces heat shock protein 70 (HSP70) release and activates MyD88 to mediate the adjuvant effects. Physical radiofrequency can potentially be a safe and potent adjuvant to augment protein/subunit vaccine-induced humoral and cellular immune responses.
Highlights
Protein/subunit vaccines often require external adjuvants to induce protective immunity
Dr Matzinger proposed danger model in 1994 to explain adaptive immunity could be driven by tissue stress, which led to identification of different endogenous danger signals, such as heat shock proteins (HSPs), uric acid, adenosine triphosphate (ATP), double-strand DNA13,14
We find non-invasive RF treatment induces local inflammation, enhances antigen uptake and maturation of dendritic cells (DCs) in the skin and draining lymph nodes, and significantly augments ID ovalbumin (OVA) and recombinant hemagglutinin-induced humoral and cellular immune responses with RF adjuvant (RFA) effects non-inferior to widely used chemical adjuvants
Summary
Protein/subunit vaccines often require external adjuvants to induce protective immunity. Physical adjuvants use physical energies rather than chemicals to stimulate tissue stress and endogenous danger signal release to boost vaccination. We show non-invasive radiofrequency can increase protein antigen-induced humoral and cellular immune responses with adjuvant effects comparable to widely used chemical adjuvants. Physical radiofrequency can potentially be a safe and potent adjuvant to augment protein/subunit vaccine-induced humoral and cellular immune responses. Physical adjuvants use physical energies rather than chemicals to stimulate tissue stress to enhance vaccine-induced immune responses. Most of the physical adjuvants reported to date still remain in the preclinical stages, the safety and potency of physical adjuvants prompted us to explore whether other types of physical energies could induce similar or better adjuvant effects by stimulation of different types of tissue stress and innate immune responses
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