Type I IFN as a Natural Adjuvant for a Protective Immune Response: Lessons from the Influenza Vaccine Model

Abstract

The identification of natural adjuvants capable of selectively promoting an efficient immune response against infectious agents would represent an important advance in immunology, with direct implications for vaccine development, whose progress is generally hampered by the difficulties in defining powerful synthetic adjuvants suitable for clinical use. Here, we demonstrate that endogenous type I IFN is necessary for the Th1 type of immune response induced by typical adjuvants in mice and that IFN itself is an unexpectedly powerful adjuvant when administered with the human influenza vaccine, for inducing IgG2a and IgA production and conferring protection from virus challenge. The finding that these cytokines, currently used in patients, are necessary for full expression of adjuvant activity and are sufficient for the generation of a protective immune response opens new perspectives in understanding the basis of immunity and in vaccine development.

Selective responsiveness to common gamma chain cytokines in peripheral blood‐derived cytotoxic T lymphocytes induced by Melan‐A/MART‐127–35targeted active specific immunotherapy

“…Most interestingly, IL-15 is produced by dendritic cells upon stimulation with IFN type I. 41 This cytokine is not only frequently used in the treatment of metastatic melanoma but it has also been shown to provide adjuvancy in the induction of humoral and CTL responses [42][43][44] and to promote in experimental models of infection or cancer, the expansion of CD8þ T cells with a memory phenotype. 45 These immunoregulatory effects might be, at least in part, attributed the induction of paracrine IL-15 production.…”

MF59 and Pam3CSK4 Boost Adaptive Responses to Influenza Subunit Vaccine through an IFN Type I-Independent Mechanism of Action

“…It has been proposed that the best strategy to boost subunit flu vaccine formulation is to restore IFN type I-associated activities that are lost during the purification process. Accordingly, coadministration of type I rIFN with a subunit influenza vaccine in mice was shown to increase protection against virus challenge (7). Alternatively, subunit flu vaccine formulation immunogenicity could be restored by incorporation of IFN inducers such as the TLR9 agonist (5).…”

Intranasal co-delivery of IL-6 gene enhances the immunogenicity of anti-caries DNA vaccine

“…Recently, studies have focused on the use of cytokines as intranasal vaccine adjuvants to enhance the immunogenicity of the DNA vaccine because of their potent effects on innate and adaptive immunity as well as functional diversity of immune responses. Studies have shown that cytokines, such as IL-12 [13,14] , IL-2 [15] , IL-15 [16] , type I interferon (IFN) [17,18] , IL-1 [19] , IL-6 [20] , and granulocyte-macrophage colony-stimulating factor (GM-CSF) [21] , enhanced antigen-specific immunity following delivery with different antigens.…”