Lipidation of NOD2 agonists with adamantane and stearoyl moieties differentially regulates their In vivo adjuvant activity

Guzelj, Samo (avtor), Šišić, Marcela (avtor), Bizjak, Špela (avtor), Frkanec, Leo (avtor), Frkanec, Ruža (avtor), Jakopin, Žiga (avtor)

NOD2 is an innate immune receptor that constitutes an important target for the development of small molecule immunopotentiators with great potential to be used as vaccine adjuvants. We report here the results of an in vivo study of the adjuvant properties of a desmuramylpeptide NOD2 agonist SG29 and its lipidated analogs featuring an adamantyl moiety or a stearoyl group. These compounds have been synthesized, incorporated into liposomes, and evaluated for their in vivo adjuvant activity. The characterization of liposome formulations of examined compounds revealed that their size increased in comparison to that of empty liposomes. The introduction of a stearoyl or an adamantane lipophilic anchor into the structure of SG29, to produce SG115 and ZSB63, respectively, substantially improved the in vivo adjuvant activity. Of note, the attachment of the stearoyl moiety produced a Th2-biased immune response, while the incorporation of the adamantyl moiety greatly enhanced the production of total IgG but mostly augmented the production of IgG2a antibodies, which indicated a shift toward a Th1 immune response. The identified bona fide capacity of ZSB63 to initiate a cellular immune response thus highlights its untapped potential as an alternative vaccine adjuvant.

• Jezik: Angleški jezik
• Ključne besede: NOD2 agonist, vaccine adjuvant, adamantane, immunopotentiators, desmuramylpeptides
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 9 str.
• Številčenje: Vol. 14, iss. 12, art. 2755
• PID: 20.500.12556/RUL-143240
• UDK: 615.4:54:616-097
• ISSN pri članku: 1999-4923
• DOI: 10.3390/pharmaceutics14122755
• COBISS.SI-ID: 133033219
• Datum objave v RUL: 09.12.2022

Gradivo je del revije

• Naslov: Pharmaceutics
• Skrajšan naslov: Pharmaceutics
• Založnik: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: agonisti NOD2, adjuvans za cepivo, adamantan, imunopotenciatorji, desmuramilpeptidi