Vaccines and antivirals are the primary strategies used to combat viral infections in humans and emerging pandemics. HIV-1, influenza and more recently, the emergence of Zika and SARS-CoV-2, pose significant challenges. For HIV-1, infected individuals harbor a substantial array of HIV-1 variants, a situation that presents a daunting challenge for developing vaccines and therapies. Similarly, the worldwide variability in flu reservoirs makes it difficult to predict which flu strain might acquire the ability to infect the human population, and due to the narrow timeframe between detecting a human infection and the “predict and produce” method for generating the vaccine each season, current influenza vaccines will likely be inadequate for preventing the next flu pandemic. Furthermore, transmission of viruses form mosquitos, such as Zika or from animals, such as SAR-CoV-2 pose a constant threat and new vaccine and antiviral technologies capable or rapidly responding to these threats are urgently needed. In an effort to address these issues, we are investigating new vaccine and antiviral concepts aimed at achieving broader, more universal protection against a wider range of highly variable viruses. Toward this goal, we have designed a therapeutic HIV DNA vaccine that when administered in combination with antiretroviral drugs to nonhuman primates infected with a primary isolate of SIV, induces profound control of viral replication that persists after antivirals are withdrawn. Viral control in this model correlated with strong mucosal CD8 responses localized in the gut, and this finding has more recently led us to investigate new DNA vaccine approaches that can more precisely focus CD8 against highly conserved epitopes and novel genetic adjuvants that can localize these responses to the gut, which is a primary source of residual virus. Similarly, using DNA and RNA vaccines and antivirals designed to precisely target highly conserved regions in influenza, we have shown significant protection against a wide range of influenza strains in mice, ferrets and nonhuman primates. More recently, we have shown that DNA and RNA vaccines can be rapidly developed in response to an emerging pandemic such as COVID-19. These studies demonstrate the feasibility of these new platforms for achieving broad protection against HIV and influenza and as a rapid response to emerging pandemics.. Studies currently in progress in the Fuller lab aim to elucidate mechanisms of protection mediated by these strategies and investigate various approach including novel adjuvants, DNA and RNA vaccine delivery approaches and combinatorial regimens to further improve these outcomes. Results from our work has resulted in over a dozen patents and two start-up biotechnology companies.
Representative publications (within the last 5 years):
- O’Connor, MA, Munson PV, Dross S, Tunggal HC, Lewis TB, Osborn J, Peterson C, Jerome KR, Kiem, H-P, Bagley KC, Mullins JI, Fuller DH (2021). A gut reaction to SIV and SHIV infection: Lower viremia and greater viral suppression during cART is associated with less gut immune dysregulation. Viruses 2021 13 (8) 1609; https://doi.org/10.3390/v13081609
- Tunggal HC, Munson PV, O’Connor MA, Hajari N, Dross SE, Bratt D, Fuller JT, Bagley K, Fuller DH (2021). Effects of therapeutic vaccination on the control of SIV in rhesus macaques with variable responsiveness to antiretroviral drugs. PLoS One 2021 Jun 17;16(6):e0253265. doi: 10.1371/journal.pone.0253265. PMID: 34138927.
- Wood MP, Jones CI, Lippy A, Oliver BG, Walund B, Francer KA, Fisher BS, Wright PJ, Fuller JT, Murpap P, Habib J, Mavigner M, Chahroudi A, Sather DN, Fuller DH, Sodora DL (2021). Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macques. PLoS Pathog. 2021 May 7;17(5):e1009575. doi: 10.1371/journal.ppat.1009575. PMID: 33961680.
- Malherbe DC, Vang L, Mendy J, Barnett PT, Spencer D, Reed JS, Kareko BW, Sather DNN, Pandey S, Wibmr CK, Robins H, Fuller DH, Park B, Lakhashe SK, Wilson JM, Axthelm MK, Ruprecht RM, Moore P, Sacha JB, Hessell AJ, Alexander J, Haigwood NL (2021). Modified adenovirus prime-protein boost clade C HIV vaccine strategy results in reduced viral DNA in blood and tissues following Tier 2 SHIV challenge. Frontiers Immunology doi: 10.3389/fimmu.2020.626464. PMID: 33658998.
- Manuzak JA, Broedlow C, Osborn JM, Gustin AT, Sandra Dross S, O’Connor MA, Coronado E, Barnette P, Hensley-McBain T, Zevin AS, Muir R, Roderer A, Wangari S, Iwayama N, Ahrens CY, Smedley J, Moats C, Lynch RM, Haddad EK, Haigwood NL, Fuller DH, Klatt NR (2021). Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques. NPJ Vaccines 6(1):34. doi: 10.1038/s41541-021-00298-4, PMID: 33707443.
- Guerriero KA, Murnane RD, Malinowski CM, Baldessari A, Jeffery DA, Lewis TB, Brown B, Fuller DH, O’Connor MA (2020). Recrudescence of Natural Coccidioidomycosis during Combination Antiretroviral Therapy in a Pigtail Macaque Experimentally Infected with Simian Immunodeficiency Virus. AIDS Res Hum Retroviruses. 2020 Dec 23;. doi: 10.1089/AID.2020.0228. PMID: 33356854
- Linsky TW, Vergara R, Codina N, Nelson JW, Walker MJ, Su W, Barnes CO, Hsiang T-Y, Esser-Nobis K, Yu K, Reneer ZB, Hou YJ, Priya T, Mitsumoto M, Pong A, Lau UY, Mason ML, Chen J, Chen A, Berrocal T, Peng H, Clairmont NS, Castellanos J, Lin Y-R, Josephson-Day A, Baric RS, Fuller DH, Walkey CD, Ross, TM, Swanson R, Bjorkman PJ, Gale Jr., M, Blancas-Mejia, LM, Yen H-L, Silva, D-A (2020). De novo design of ACE2 protein decoys to neutralize SARS-CoV-2. Science Nov 5; eabe0075.doi: 10.1126/science.abe0075. PMID: 32793910.
- Walls AC, Fiala B, Schäfer A, Wrenn S, Pham MN, Murphy M, Tse LV, Shehata L, O'Connor MA, Chen C, Navarro MJ, Miranda MC, Pettie D, Ravichandran R, Kraft JC, Ogohara C, Palser A, Chalk S, Lee EC, Guerriro K, Kepl E, Chow C, Sydeman C, Hodge EA, Brown B, Fuller JT, Dinnon KH, Gralinksi LE, Leist SR, Gully KL, Lewis TB, Guttman M, Chu HY, Lee KK, Fuller DH, Baric RS, Kellam P, Carter L, Pepper M, Sheahan TP, Veesler D, King N (2020). Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell Oct 31;S0092-8674(20)31450-1. doi: 10.1016/j.cell.2020.10.043. PMID: 33160446.
- Powell R, Weiss S, Fox A, Liu X, Itri V, Jiang X, Luo C, Spencer D, Pandey S, Cheever T, Fuller D, Totrov M, Hessell A, Haigwood N, Kong X-P, Zolla-Pazner S (2020). An HIV vaccine targeting the V2 region of Envelope induces a highly durable polyfunctional Fc-mediated antibody response in rhesus macaques, J Virol. Aug 17;94(17):e01175-20. doi: 10.1128/JVI.01175-20. PMID: 32554699.
- Erasmus, JH, Khandhar AP, Walls AC, Hemann EA, O’Connor MA, Murapa P, Archer J, Leventhal S, Fuller, J, Lewis T, Draves KE, Randall S, Guerriero KA, duthie MS, Carter D, Reed SG, Hawman DW, Feldmann H, Gale M Jr., Veesler D, Berglund P, Fuller DH (2020). An alphvirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates. Sci Transl Med Aug 5;12(555): eabc9396. doi: 10.1126/scitranslmed.abc9396. PMID: 32690628.
- Malherbe, DC, Wibmer CK, Nonyane M, Reed, J, Sather DN, Spencer D, Schuman JT, Guo B, Pandey S, Robins H, Park B, Fuller DH, Sacha JB, Moore PL, Hessell AJ, Haigwood NL (2020). Rapid induction of multifunctional antibodies in rabbits and macaques by clade C HIV-1 CAP257 envelopes circulating during epitope-specific neutralization breadth development. Front Immunol. Jun 2;11:984. doi: 10.3389/fimmu.2020.00984.PMID: 32582155.
- Erasmus, JH, Fuller DH (2020). Preparing for pandemics: RNA vaccines at the forefront. Mol Ther. Jul 8;28(7):1559-1560. doi: 10.1016/j.ymthe.2020.06.017. PMID: 32579882.
- Fuller DH and PJ Berglund (2020). Amplifying RNA Vaccine Development. N Engl J Med, Jun 18;382(25):2469-2471. doi: 10.1056/NEJMcibr2009737. PMID: 32558474.
- Wood MP, Wood L, Templeton M, Fisher B, Lippy A, Joes CI, Arlehamn L, Fuller J, Murapa P, Jaspan H, Fuller DH, Sodora D (2020). Transient immune activiation associated with BCG vaccination of infant rhesus macaques is not sufficient to influence oral simian immunodeficiency virus infection. JID doi.org/10.1093/infdis/jiz382; PMID: 31605528.
- Hessell AJ, Powell R, Jiang X, Luo C, Weiss S, Dussupt V, Itri V, Fox A, Shapiro MB, Pandey S, Cheever T, Fuller DH, Park B, Krebs SJ, Totrov M, Haigwood NL (2019). Multimeric epitope-scaffold HIV vaccine target V1V2 and differentially tune polyfunctional antibody responses. Cell Reports 28 (4): 877-895 PMID: 31340151.
- O’Connor MA, Munson PV, Tunggal HC, Hajari N, Lewis TB, Bratt D, Moats C, Smedley J, Bagley KC, Mullins JI, Fuller DH (2019). Mucosal T helper 17 and T regulatory cell homeostasis correlates with acute SIV viremia and responsiveness to antiretroviral therapy in macaques. AIDS Research and Human Retroviruses; doi.org/10.1089/aid.2018.0184, PMID: 30398361
- O’Connor MA, Tisoncik-Go J, Lewis TB, Miller CJ, Bratt D, Moats CR, Smedley J, Klatt NR, Gale Jr, M, Fuller DH (2018). Zika viral persistence and tissue tropism in pigtail macaques is driven by early cellular innate immune responses. Nature Communications: 3371; doi: 10.1038/s41467-018-05826-w, PMID: 30135445
- Ramsingh AI, Gray SJ, Reilly A, Koday M, Bratt D, Koday MT, Murnane R, Smedley J, Hu Y, Munson PV, Messer A, Fuller DH (2018). Sustained AAV9-mediated expression of a non-self protein in the CNS of non-human primates after immunomodulation, PLoS One Jun 6;13(6):e0198154. doi: 10.1371/journal.pone.0198154. PMID: 29874260.
- Munson PV, Tunggal H, O’Connor M, Bratt D, May A, Wangari S, Agricola B, Smedley J, Fuller JT, Kulkarni V, Felber, BK, Pavlakis GN, Mullins JI, Fuller DH (2018). Therapeutic conserved elements (CE) DNA vaccine induces strong T-cell responses against highly conserved viral sequences during chronic viral infection. Human Vaccines and Immunotherapy DOI: 10.1080/21645515.2018.1448328; PMID: 29648490
- Koday MT, Leonard J, Fuller JT, Bratt D, Koday M, Fuller DH (2017). Multivalent Influenza DNA Vaccine Induces Potent Antibodies and Broadly-Specific T Cell Responses in Non-human Primates, PLoS One https://doi.org/10.1371/journal.pone.0189780. PMID: 29267331
- Chevalier A, Silva D-A, Rocklin G-J, Hicks DR, Vergara R, Murapa P, Bernard SM, Zhang L, Lam K-H,Yao G, Bahl CD, Miyashita S-I, Inna G, Fuller JT, Koday MT, Jenkins C, Colvin T, Carter L, Bohn A, Bryan CM, Fernandez-Velasco DA, Stewart L, Dong M, Huang X, Jin R, Wilson IA, Fuller DH, Baker D (2017). Massively parallel de novo protein design for targeted therapeutics, Nature 550 (7674): 74-79; DOI: doi:10.1038/nature23912, PMID: 28953867.
- Strauch EM, Bernard SM, Bohn AJ, Lee PS, Anderson, CE, Nieusma T, Holstein CA, La D, Garcia NK, Hooper KA, Ravichandran R, Nelson J, Sheffler W, Bloom JD, Lee KK, Ward AB, Yager P, Fuller DH, Wilson IA, Baker D (2017). Design of trimeric influenza neutralizing proteins targeting the hemagglutinin receptor binding site. Nature Biotechnology 35(7): 667-71. DOI:10.1038/nbt.3907. PMID: 28604661.
- Dross SE, Munson P, Kim, SE, Bratt, D, Gervassi, A, Fuller DH, Horton, H (2016). Kinetics of myeloid derived suppressor cell frequency and function during SIV infection and combination antiretroviral therapy. J Immunol. 198(2): 757-766; DOI: 10.4049/jimmunol.1600759; PMID: 27974456.
- Smedley, J, Macalister R, Wangari S, Gathuka M, Ahrens J, Iwayama N, May D, Bratt D, Munson P, Lifson J, Fuller DH (2016). Laparoscopic Technique for Serial Collection of Para-Colonic, Left Colic, and Inferior Mesenteric Lymph Nodes in Macaques. PLoS One 11(6): e0157535. doi:10.1371/journal.pone.0157535. PMID: 27309717, PMCID: PMC 4911112.
- McBurney SP, Sunshing JE, Huynh GS, Sutton WF, Fuller DH, Haigwood NL, Messer WB (2016). Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates. Vaccine 24;34(30):3500-7. doi: 10.1016/j.vaccine.2016.03.108. PMID: 27085173.
- Koday MT, Nelson J, Chevalier A, Koday M, Kalinoski H, Stewart L, Carter L, Nieusma T, Lee PS, Ward AB, Wilson IA, Dagley A, Smee DF, Baker D, Fuller DH (2016). A Computationally Designed Hemagglutini Stem-Binding Protein Provides In Vivo Prorection from Influenza Independent of a Host Immune Response. PLoS Pathog: doi: 10.1371/journal.ppat.1005409. PubMed PMID: 26845438; PMCID: PMC4742065.
Extended list of publications:
Diversity and Inclusive Trainings Taken:
I am committed to developing policies and outreach strategies at UW to support URMs trainees, staff and faculty at UW. This includes regular meetings and connecting with other diversity groups and identifying opportunities for fellowships and awards. I am a member of the Latinx Faculty Staff Association (LFSA) and in 2019 and 2020 I was honored to receive the UW Latinx Faculty Excellence in Research Awards. I also recently contributed to LFSA’s 2020 book entitled Latinx Experience in Academia: Charting the paths of Latinx faculty at the University of Washington which tells the stories of UW Latinx faculty career pathways and provides advice to URM students, postdocs and faculty.