TY - JOUR
T1 - Adjuvant lipidoid-substituted lipid nanoparticles augment the immunogenicity of SARS-CoV-2 mRNA vaccines
AU - Han, Xuexiang
AU - Alameh, Mohamad Gabriel
AU - Butowska, Kamila
AU - Knox, James J.
AU - Lundgreen, Kendall
AU - Ghattas, Majed
AU - Gong, Ningqiang
AU - Xue, Lulu
AU - Xu, Ying
AU - Lavertu, Marc
AU - Bates, Paul
AU - Xu, Junchao
AU - Nie, Guangjun
AU - Zhong, Yi
AU - Weissman, Drew
AU - Mitchell, Michael J.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/9
Y1 - 2023/9
N2 - Lipid nanoparticle (LNP)-formulated messenger RNA (mRNA) vaccineare a promising platform to prevent infectious diseases as demonstrated by the recent success of SARS-CoV-2 mRNA vaccines. To avoid immune recognition and uncontrolled inflammation, nucleoside-modified mRNA is used. However, such modification largely abrogates the innate immune responses that are critical to orchestrating robust adaptive immunity. Here we develop an LNP component—an adjuvant lipidoid—that can enhance the adjuvanticity of mRNA-LNP vaccines. Our results show that partial substitution of ionizable lipidoid with adjuvant lipidoid not only enhanced mRNA delivery, but also endowed LNPs with Toll-like receptor 7/8-agonistic activity, which significantly increased the innate immunity of the SARS-CoV-2 mRNA-LNP vaccine with good tolerability in mice. Our optimized vaccine elicits potent neutralizing antibodies against multiple SARS-CoV-2 pseudovirus variants, strong Th1-biased cellular immunity, and robust B cell and long-lived plasma cell responses. Importantly, this adjuvant lipidoid substitution strategy works successfully in a clinically relevant mRNA-LNP vaccine, demonstrating its translational potential.
AB - Lipid nanoparticle (LNP)-formulated messenger RNA (mRNA) vaccineare a promising platform to prevent infectious diseases as demonstrated by the recent success of SARS-CoV-2 mRNA vaccines. To avoid immune recognition and uncontrolled inflammation, nucleoside-modified mRNA is used. However, such modification largely abrogates the innate immune responses that are critical to orchestrating robust adaptive immunity. Here we develop an LNP component—an adjuvant lipidoid—that can enhance the adjuvanticity of mRNA-LNP vaccines. Our results show that partial substitution of ionizable lipidoid with adjuvant lipidoid not only enhanced mRNA delivery, but also endowed LNPs with Toll-like receptor 7/8-agonistic activity, which significantly increased the innate immunity of the SARS-CoV-2 mRNA-LNP vaccine with good tolerability in mice. Our optimized vaccine elicits potent neutralizing antibodies against multiple SARS-CoV-2 pseudovirus variants, strong Th1-biased cellular immunity, and robust B cell and long-lived plasma cell responses. Importantly, this adjuvant lipidoid substitution strategy works successfully in a clinically relevant mRNA-LNP vaccine, demonstrating its translational potential.
UR - https://www.scopus.com/pages/publications/85162889028
U2 - 10.1038/s41565-023-01404-4
DO - 10.1038/s41565-023-01404-4
M3 - 文章
C2 - 37365276
AN - SCOPUS:85162889028
SN - 1748-3387
VL - 18
SP - 1105
EP - 1114
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 9
ER -
