title: Co-Administration of Lipid Nanoparticles and Sub-Unit Vaccine Antigens Is Required for Increase in Antigen-Specific Immune Responses in Mice.
abstract: A vast body of evidence suggests that nanoparticles function as potent immune-modulatory agents. We have previously shown that Merck proprietary Lipid NanoParticles (LNPs) markedly boost B-cell and T-cell responses to sub-unit vaccine antigens in mice. To further evaluate the specifics of vaccine delivery and dosing regimens in vivo, we performed immunogenicity studies in BALB/c and C57BL/6 mice using two model antigens, Hepatitis B Surface Antigen (HBsAg) and Ovalbumin (OVA), respectively. To assess the requirement for co-administration of antigen and LNP for the elicitation of immune responses, we evaluated immune responses after administering antigen and LNP to separate limbs, or administering antigen and LNP to the same limb but separated by 24 h. We also evaluated formulations combining antigen, LNP, and aluminum-based adjuvant amorphous aluminum hydroxylphosphate sulfate (MAA) to look for synergistic adjuvant effects. Analyses of antigen-specific B-cell and T-cell responses from immunized mice revealed that the LNPs and antigens must be co-administered-both at the same time and in the same location-in order to boost antigen-specific immune responses. Mixing of antigen with MAA prior to formulation with LNP did not impact the generation of antigen-specific B-cell responses, but drastically reduced the ability of LNPs to boost antigen-specific T-cell responses. Overall, our data demonstrate that the administration of LNPs and vaccine antigen together enables their immune-stimulatory properties.
authors.affiliation: Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA. elizabeth_thoryk@merck.com.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thoryk
authors.affiliation: Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA. gokul.swaminathan@merck.com.
authors.forename: Gokul
authors.initials: G
authors.lastname: Swaminathan
authors.affiliation: Medical Affairs, Global Human Health, Merck & Co., Inc., Kenilworth, NJ 07033, USA. steven_meschino@merck.com.
authors.forename: Steven
authors.initials: S
authors.lastname: Meschino
authors.affiliation: Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA. kara_cox@merck.com.
authors.forename: Kara S
authors.initials: KS
authors.lastname: Cox
authors.affiliation: Pharmaceutical Sciences, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA. marian_gindy@merck.com.
authors.forename: Marian
authors.initials: M
authors.lastname: Gindy
authors.affiliation: Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA. DCasimiro@aeras.org.
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.affiliation: Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA. Andrew_bett@merck.com.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bett
keywords: adjuvants; alum; formulation; lipid nanoparticles; vaccines