A novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens. Issue 1 (2nd January 2016)

• Record Type: Journal Article
• Authors: Swaminathan, Gokul; Thoryk, Elizabeth A.; Cox, Kara S.; Meschino, Steven; Dubey, Sheri A.; Vora, Kalpit A.; Celano, Robert; Gindy, Marian; Casimiro, Danilo R.; Bett, Andrew J.
• Is Part Of: Vaccine. Volume 34:Issue 1(2016)
• Page Start: 110
• Page End: 119
• Publication Date: 2016-01-02
• Subjects: Lipid nanoparticle -- TLR9 agonist -- Adjuvant -- Subunit vaccine -- CD8 T cell response; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.10.132
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: Sub-unit vaccines are primarily designed to include antigens required to elicit protective immune responses and to be safer than whole-inactivated or live-attenuated vaccines. But their purity and inability to self-adjuvant often result in weaker immunogenicity. Emerging evidence suggests that bio-engineered nanoparticles can be used as immunomodulatory adjuvants. Therefore, in this study we explored the potential of novel Merck-proprietary lipid nanoparticle (LNP) formulations to enhance immune responses to sub-unit viral antigens. Immunization of BALB/c and C57BL/6 mice revealed that LNPs alone or in combination with a synthetic TLR9 agonist, immune-modulatory oligonucleotides, IMO-2125 (IMO), significantly enhanced immune responses to hepatitis B virus surface antigen (HBsAg) and ovalbumin (OVA). LNPs enhanced total B-cell responses to both antigens tested, to levels comparable to known vaccine adjuvants including aluminum based adjuvant, IMO alone and a TLR4 agonist, 3-O-deactytaled monophosphoryl lipid A (MPL). Investigation of the quality of B-cell responses demonstrated that the combination of LNP with IMO agonist elicited a stronger Th1-type response (based on the IgG2a:IgG1 ratio) than levels achieved with IMO alone. Furthermore, the LNP adjuvant significantly enhanced antigen specific cell-mediated immune responses. In ELISPOT assays, depletion of specific subsets of T cells revealed that the LNPs elicited potent antigen-specific CD4 + and CD8 + T cell responses. Intracellular FACS analyses revealed that LNP and LNP + IMO formulated antigens led to higher frequency of antigen-specific IFNγ + TNFα + IL-2 +, multi-functional CD8 + T cell responses, than unadjuvanted vaccine or vaccine with IMO only. Overall, our results demonstrate that lipid nanoparticles can serve as future sub-unit vaccine adjuvants to boost both B-cell and T-cell responses in vivo, and that addition of IMO can be used to manipulate the quality of immune responses.