The Chen lab focuses on developing novel vaccine adjuvants and delivery platforms to improve drug and vaccine efficacy. We emphasize on multidisciplinary approaches to address challenges in drug/vaccine delivery and vaccine adjuvants. In particular, we are developing novel physical and chemical adjuvants to augment vaccine-induced immune responses without provoking overt inflammation and high-density flagellin-displayed virus-like particle platform with high immunogenicity, versatility, and safety to support vaccine development. Other interests include the exploration of minimally invasive techniques (e.g., laser) to facilitate sustained transdermal drug delivery and more immunogenic vaccination, the use of omics tools to study adjuvantation mechanisms, and the development of effective adjuvants to boost mRNA vaccination.
Professor Xinyuan Chen and Ph.D. student Yiwen Zhao work in Chen’s lab on a virus-like particle platform they hope will help lead to a universal flu vaccine.
News
2022-2023
Welcome Labone Akter to join our lab as a PhD student.
Congrats Yibo for his poster presentation titled ‘Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant’ at Research and Education Poster Abstracts Presented at the 123rd Annual Meeting of the American Association of Colleges of Pharmacy, Grapevine, TX.
Congratulations! Yibo’s conference abstract titled ‘Comparative tissue proteomics reveals unique action mechanisms of vaccine adjuvants’ was selected for oral presentation by American Association of Pharmaceutical Scientists Northeast Regional Discussion Group 25th Annual Conference, Queens, NY.
Congrats Xinliang for her poster presentation titled ‘Overcoming Aging-Associated Poor Influenza Vaccine Responses with CpG 1018 Adjuvant’ at National IDeA Symposium of Biomedical Research Excellence (NISBRE) 2022 Infectious Disease (Virtual).
Congrats Yibo being awarded the College Teaching Assistant Excellence Award of 2023.
2021-2022
Welcome Xinliang Kang (stuck in China for a whole year due to Covid) to come to our lab for her PhD study.
Congrats! Yiwen was offered a company position in Codagenix Inc., Farmingdale, NY/Cambridge, MA.
Congratulations! Jewel was offered a position in Dr. Bing Chen lab at Harvard Medical School.
Congratulations! Yiwen’s first authored paper titled ‘Flagellin/virus-like particle hybrid platform with high immunogenicity, safety, and versatility for vaccine development’ was accepted for publication in ACS Applied Materials & Interfaces.
Welcome Dr. Jayachandra Reddy Nakkala (Reddy) to join our lab as a postdoctoral fellow.
2020-2021
Congrats! Yiwen successfully defended her PhD thesis in August.
Congratulations! Zhuofan was offered a position in Abogen Biosciences (China).
Congrats! Yiwen’s abstract titled “Improving immunogenicity and safety of flagellin as vaccine carrier by high-density display on virus-like particle surface”, submitted for “12th Annual Jarowski Symposium”, has been selected for an oral presentation.
Congratulations! Jewel for multiple achievements.
Receiving MARC U* Star Internal Funding Grant in April
Receiving second URI Undergraduate Research Grant in May
Presented the research done last year at the Annual MARC U*Star Symposium in May
Accepted to Harvard SHURP and the story posted in a different page
Congrats! Michael was awarded Excellence in Academic Achievements (GPA 4.0).
2019-2020
Yiwen presented her poster entitled ‘Improving immunogenicity and safety of flagellin as vaccine carrier by high-density display on hepatitis b core virus-like particle surface’ at the 14th Vaccine Conference – Online Edition on Sep. 28-29, 2020.
Congratulations! Jewel was awarded an Undergraduate Research grant titled ‘Develop Virus-Like Particle-Based COVID-19 Vaccine’ with project period from 1/1/2021-4/30/2021.
Congratulations! Jewel’s Honors Project Proposal has been accepted as a 6 credit HPR 401/402 independent study project for Spring-Fall 2021. Her proposal is titled ‘Generation of a More Immunogenic FH VLP Platform to Support Covid-19 Vaccine Development’.
Welcome Michael Dailey to do Independent Study in our lab in the spring semester of 2021.
Safe and potent adjuvants are highly demanded to aid in development of new and improved vaccines. Due to the slow progress in developing novel chemical adjuvants, we took a different approach to develop physical radiofrequency adjuvant (RFA) to boost vaccination. RFA emits alternating electromagnetic fields in the skin surface and induce tissue stress to alert innate immune systems to enhance intradermal vaccine-induced immune responses. Significant progress was made in evaluation of its safety and potency to boost intradermal influenza vaccination with several major findings: 1) RFA shows similar potency to AddaVax adjuvant in potentiation of influenza vaccine-induced humoral immune responses; 2) RFA has potent dose-sparing effects and can aid nanograms of influenza vaccine to induce protective immunity; 3) RFA enables the induction of cross-protective immunity; 4) RFA induces transient low-level local inflammation and minimally changes local tissue proteome, in sharp contrast to traditional chemical adjuvants; 5) HSP70 and MyD88 play crucial roles in RFA effects. Currently, we try to understand how HSP70 and MyD88 contribute to the potent and low-inflammatory RFA effects and evaluate the potential of RFA for human use. The ultimate goal of this project is to develop a highly potent RFA to safely boost intradermal vaccination without inducing significant local or systemic adverse reactions.
High-density flagellin-displayed hepatitis b core (FH) virus-like particle (VLP) platform for vaccine development
Virus-like particles (VLPs) simulate natural viruses and are able to induce potent humoral and cellular immune responses. VLPs have been attractive vaccine delivery platforms due to their high immunogenicity and safety. Hepatitis b core (HBc) VLPs have been widely explored to display foreign antigens by insertion into its c/e1 loop. Yet, only small antigenic peptides can be successfully inserted without interference with its self-assembly into VLPs. Flagellin is a toll-like receptor (TLR) 5 agonist and has been also explored as highly immunogenic vaccine carriers. The close proximity of N- and C-terminal domains of flagellin allows its successful insertion into the c/e1 loop of HBc without affecting its self-assembly into VLPs. The resulting flagellin-displayed HBc (FH) VLPs show high immunogenicity, safety, and versatility to support vaccine development. Currently, we are taking advantage of the highly immunogenic FH VLP platform to develop M2e-based universal influenza vaccine.
Laser generates skin microchannels to facilitate transdermal drug delivery and vaccination
This project explores ablative fractional laser as a minimally invasive tool to generate skin microchannels to facilitate transcutaneous drug delivery and vaccination.
Various patch systems are developed to allow powder drugs to be loaded for convenient delivery via laser-generated skin microchannels. Laser-based powder delivery takes advantage of water evaporated from skin microchannels to dissolve topical drugs to initiate the dual-phase delivery (dissolution/diffusion). Laser-based powder delivery enables highly efficient delivery of water-soluble chemical drugs and also biologics drugs. Such a dual-phase delivery platform can sustain drug release from hours to a week, often resulting in improved drug availability and therapeutic efficacy.
Laser-based powder delivery can also be used for high-efficient transcutaneous vaccination. Laser-based power vaccination eliminates needle injection and has the ability to minimize vaccine/adjuvant-induced local adverse reactions by delivery of a small fraction of doses to skin microchannels that are surrounded by unaffected skin with full recovery ability. Laser-based powder vaccination can also elicit more potent immune responses than needle-based injection delivery by induction of tissue stress to alert local innate immune systems of danger.
Proteomics aids in elucidation of vaccine adjuvant mechanisms
One obstacle in developing safer and more potent adjuvants is the lack of understanding about adjuvant mechanisms. Significant progress has been made in the last two decades in elucidation of mechanisms of commonly used adjuvants. Despite these advances, a complete understanding about their action mechanisms is still elusive. This project takes advantage of omics techniques with a current focus on proteomics to elucidate mechanisms of vaccine adjuvants and their synergistic effects.
mRNA evolves as a novel vaccine platform with unique advantages, such as quick production, low risk of genome integration, and high immunogenicity as can be seen from Moderna and Pfizer mRNA-based Covid-19 vaccines. Due to its high immunogenicity, no adjuvants have been added to further boost mRNA vaccine efficacy. Yet, adjuvants may be needed to develop mRNA vaccines against certain infectious diseases or cancer. As of such, this project explores effective adjuvants from currently available ones and develop novel adjuvants to safely and potently boost mRNA vaccination.
Publications
2023
Li Y, Chen X#. Protocol for preparing murine tissue for comparative proteomics study of vaccine adjuvant mechanisms. STAR Protoc. 2023 Jul 1;4(3):102396. doi: 10.1016/j.xpro.2023.102396.
Li Y, Chen X#. CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein. Vaccines (Basel). 2023 Mar 14;11(3):649. doi: 10.3390/vaccines11030649. PMID: 36992232 PMCID: PMC10055716
Zhao Y, Voyer J, Li Y, Kang X, Chen X#. Laser microporation facilitates topical drug delivery: a comprehensive review about preclinical development and clinical application. Expert Opin Drug Deliv. 2023 Jan;20(1):31-54. doi: 10.1080/17425247.2023.2152002. Epub 2022 Dec 15.
2022
Chen X#. Emerging adjuvants for intradermal vaccination. Int J Pharm. 2022 Dec 28;632:122559. doi: 10.1016/j.ijpharm.2022.122559. Online ahead of print.
X Kang, Y Li, Y Zhao, X Chen#. Overcoming Aging-Associated Poor Influenza Vaccine Responses with CpG 1018 Adjuvant. Vaccines (Basel). 2022 Nov 10;10(11):1894. doi: 10.3390/vaccines10111894.
Li Z, Kang X, Kim KH, Zhao Y, Li Y, Kang SM, Chen X#. Effective adjuvantation of nanograms of influenza vaccine and induction of cross-protective immunity by physical radiofrequency adjuvant. Sci Rep. 2022 Dec 8;12(1):21249. doi: 10.1038/s41598-022-25605-4.
Li Y, Li Z, Chen X#. Comparative tissue proteomics reveals unique action mechanisms of vaccine adjuvants. iScience. 2022 Dec 14;26(1):105800. doi: 10.1016/j.isci.2022.105800. eCollection 2023 Jan 20.
Zhao Y, Li Z, Voyer J, Li Y, Chen X#. Flagellin/Virus-like Particle Hybrid Platform with High Immunogenicity, Safety, and Versatility for Vaccine Development. ACS Appl Mater Interfaces. 2022 Apr 25;. doi: 10.1021/acsami.2c01028. [Epub ahead of print] PubMed PMID: 35467839.
Li Z, Kim KH, Bhatnagar N, Park BR, Jeeva S, Jung YJ, Raha J, Kang SM, Chen X#. Physical radiofrequency adjuvant enhances immune responses to influenza H5N1 vaccination. FASEB J. 2022 Mar;36(3):e22182. doi: 10.1096/fj.202101703R. PubMed PMID: 35113455; PubMed Central PMCID: PMC8928172.
2021
Li Y, Li Z, Zhao Y, Chen X#. Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant. Vaccines (Basel). 2021 Nov 24;9(12). doi: 10.3390/vaccines9121382. PubMed PMID: 34960128; PubMed Central PMCID: PMC8706500.
Li Z, Cao Y, Li Y, Zhao Y, Chen X#. Vaccine delivery alerts innate immune systems for more immunogenic vaccination. JCI Insight. 2021 Mar 9:144627. doi: 10.1172/jci.insight.144627. Online ahead of print.
Li Z, Zhao Y, Li Y, Chen X#. Adjuvantation of Influenza Vaccines to Induce Cross-Protective Immunity. Vaccines (Basel). 2021 Jan 21;9(2):75. doi: 10.3390/vaccines9020075.
2020
Zhao Y, Li Z, Zhu X, Cao Y, Chen X#. Improving immunogenicity and safety of flagellin as vaccine carrier by high-density display on virus-like particle surface. Biomaterials. 2020 Aug;249:120030.
Kakar P, Li Z, Li Y, Cao Y, Chen X#. Laser facilitates week-long sustained transdermal drug delivery at high doses. J Control Release. 2020 Mar 10;319:428-437.
2018
Cao Y, Zhu XY, Hossen MN, Kakar P, Zhao YW, Chen X#. Augmentation of vaccine-induced humoral and cellular immunity by a physical radiofrequency adjuvant. Nature Communications. 2018, 9:3695.
Research Team
Dr. Chen lab welcomes the application of undergraduate and graduate research positions from highly motivated students. If interested, please send your CV and unofficial transcripts to Dr. Chen (xchen14@uri.edu).
