Anti-Viral Antibodies

We have identified a number of highly potent human mAbs directed against CHIKV. The most potent of these mAbs demonstrated previously undescribed mechanisms of action – including cross-linking individual subunits within envelope spikes and the inhibition of viral release – likely by preventing membrane curvature formation. Identification of potent neutralizing mAbs targeting different stages of the viral lifecycle will provide prophylactic and therapeutic treatment options for CHIKV infection and disease – with a focus on vulnerable populations during epidemics.

Selected Publications:

Jin J, Simmons G. Inhibitory Antibodies Targeting Emerging Viruses: Advancements and Mechanisms. Clin Vac Immunol. (2016). 23:535-9. PMCID: PMC4933769

Fox JM, Long F, Edeling MA, Lin H, van Duijl-Richter MK, Fong RH, Kahle KM, Smit JM, Jin J, Simmons G, Doranz BJ, Crowe JE Jr, Fremont DH, Rossmann MG, Diamond MS. Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress. Cell (2015). 163:1095-107. PMCID: PMC4659373

Jin J, Liss NM, Chen D-H, Liao M, Fox JM, Shimak RM, Fong RH, Chafets D, Bakkour S, Keating S, Fomin M, Muench MO, Sherman MB, Doranz BJ, Diamond MS, Simmons G. Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis. Cell Reports (2015). 13(11):2553-64. PMCID:PMC4720387

Fong RH, Banik SS, Mattia K, Barnes T, Tucker D, Liss N, Lu K, Selvarajah S, Srinivasan S, Mabila M, Miller A, Muench MO, Michault A, Rucker JB, Paes C, Simmons G, Kahle KM, Doranz BJ. Exposure of epitope residues on the outer face of the chikungunya virus envelope trimer determines antibody neutralizing efficacy. J Virol. (2014). 88:14364-79. PMCID: PMC4249124.

Selvarajah S, Sexton S, Kahle KM, Fong RH, Mattia KA, Gardner J, Lu K, Liss NM, Salvador B, Tucker DF, Barnes T, Mabila M, Zhou X, Rossini G, Rucker JB, Sanders DA, Suhrbier A, Sambri V, Michault A, Muench MO, Doranz BJ, Simmons G. A neutralizing monoclonal antibody targeting the acid-sensitive region in chikungunya virus E2 protects from disease. PLoS Negl Trop Dis. (2013). 7:e2423. PMCID: PMC3772074.

Capon DJ, Kaneko N, Yoshimori T, Shimada T, Wurm FM, Hwang PK, Tong X, Adams SA, Simmons G, Sato TA, Tanaka K. Flexible antibodies with nonprotein hinges. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87:603-616. PMCID: PMC3309923.