A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates

Abstract

After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

Effects of different immunomodulating liposome-based adjuvants and injection sites on immunogenicity in pigs

“…We monitored IFN-γ and IL-17, as CAF01 was shown to induce a strong mixed Th1/Th17 immune response in mice and non-human primates [5], [27]. IFN-γ concentration was variable within each group, but there was a tendency towards CAF23 group producing the highest amounts of IFN-γ, even though two pigs were nonresponders (Fig 1D).…”

Pivotal role of tissue-resident memory lymphocytes in the control of mucosal infections: can mucosal vaccination induce protective tissue-resident memory T and B cells?

“…Indeed, it was reported that all-trans-retinoic acid administered by intraperitoneal route could enhance the frequency of antigen-specific memory T cells in murine intestine (67). Woodworth et al demonstrated that CAF ® 10b, a liposomal adjuvant administered by intramuscular route, could prime T cells in order to recall them in the lungs or skin using the antigen only administered by intratracheal and intradermal routes in NHP (68). If all-trans-retinoic acid or CAF ® 10b adjuvants are beneficial to induce mucosal tissueresident memory responses, it remains to be confirmed.…”