Antibody Immunity Section
Major Areas of Research
- HIV vaccines
- HIV neutralizing antibodies as drugs for prevention and treatment
- SARS-CoV-2 antibodies for prevention of COVID-19 and other coronavirus diseases
Program Description
The aims of AIMS are:
- To understand pathways of HIV broadly neutralizing antibody (bNAb) development and co-evolution with virus
- To design and test HIV Vaccines inspired by antibody-virus co-evolution studies
- To discover and characterize new HIV bNAbs with potential clinical use
- To understand SARS-CoV-2 and pan-sarbecovirus antibody development
Neutralizing antibodies, which block virus infection, are critical components of effective immune responses and the correlate of protection for many licensed vaccines. Broadly neutralizing antibodies (bNAbs) against HIV are able to recognize diverse HIV strains from around the world; eliciting bNAbs will be a crucial function of a protective vaccine. While no candidate HIV vaccine has yet succeeded in eliciting bNAbs, a fraction of people living with HIV develop them naturally. We are studying these cases to understand the way the bNAbs target HIV and how they develop over time. We previously showed that viral escape mutants drive the development of breadth in antibodies targeting the apex of the HIV Envelope protein (the viral “spike”), and identified key early changes in bNAbs targeting the HIV Env membrane-proximal external region. Work continues to understand virus-antibody co-evolution for these and other targets on HIV Env. These studies provide a blueprint for vaccine design as we strive to elicit bNAbs. Along the way, we are identifying highly potent bNAbs that may be useful as drugs for HIV prevention.
Using a similar conceptual framework and methods, we are studying antibodies in COVID-19 infected and vaccinated people. We are isolating antibodies with potential clinical use against SARS-CoV-2 and also against related coronaviruses with potential to cause the next pandemic; and studying the development of these antibodies, to improve vaccine designs.
Selected Publications
Doria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, DeKosky BJ, Ernandes MJ, Georgiev IS, Kim HJ, Pancera M, Staupe RP, Altae-Tran HR, Bailer RT, Crooks ET, Cupo A, Druz A, Garrett NJ, Hoi KH, Kong R, Louder MK, Longo NS, McKee K, Nonyane M, O’Dell S, Roark RS, Rudicell RS, Schmidt SD, Sheward DJ, Soto C, Wibmer CK, Yang Y, Zhang Z, NISC Comparative Sequencing Program, Mullikin JC, Binley JM, Sanders RW, Wilson IA, Moore JP, Ward AB, Georgiou G, Williamson C, Abdool Karim SS, Morris L, Kwong PD, Shapiro L, Mascola JR. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014 May 1;509(7498):55-62. Epub 2014 Mar 2.
Bhiman JN, Anthony C, Doria-Rose NA, Karimanzira O, Schramm CA, Khoza T, Kitchin D, Botha G, Gorman J, Garrett NJ, Abdool Karim SS, Shapiro L, Williamson C, Kwong PD, Mascola JR, Morris L, Moore PL. Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies. Nat Med. 2015 Nov;21(11):1332-6.
Doria-Rose NA, Bhiman JN, Roark RS, Schramm CA, Gorman J, Chuang GY, Pancera M, Cale EM, Ernandes MJ, Louder MK, Asokan M, Bailer RT, Druz A, Fraschilla IR, Garrett NJ, Jarosinski M, Lynch RM, McKee K, O'Dell S, Pegu A, Schmidt SD, Staupe RP, Sutton MS, Wang K, Wibmer CK, Haynes BF, Abdool-Karim S, Shapiro L, Kwong PD, Moore PL, Morris L, Mascola JR. New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency. J Virol. 2015 Oct 14;90(1):76-91.
Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schätzle S, McDaniel JR, Lai YT, Sastry M, Zhang B, Jarosinski MC, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang GY, Darko S, Driscoll JI, Druz A, Gorman J, Laboune F, Louder MK, McKee K, Mendez L, Moody MA, O'Sullivan AM, Owen C, Peng D, Rawi R, Sanders-Buell E, Shen CH, Shiakolas AR, Stephens T, Tsybovsky Y, Tucker C, Verardi R, Wang K, Zhou J, Zhou T, Georgiou G, Alam SM, Haynes BF, Rolland M, Matyas GR, Polonis VR, McDermott AB, Douek DC, Shapiro L, Tovanabutra S, Michael NL, Mascola JR, Robb ML, Kwong PD, Doria-Rose NA. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual. Immunity. 2019 Mar 19;50(3):677-691.
Pegu A, O'Connell SE, Schmidt SD, O'Dell S, Talana CA, Lai L, Albert J, Anderson E, Bennett H, Corbett KS, Flach B, Jackson L, Leav B, Ledgerwood JE, Luke CJ, Makowski M, Nason MC, Roberts PC, Roederer M, Rebolledo PA, Rostad CA, Rouphael NG, Shi W, Wang L, Widge AT, Yang ES; mRNA-1273 Study Group, Beigel JH, Graham BS, Mascola JR, Suthar MS, McDermott AB, Doria-Rose NA. Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants. Science. 2021 Sep 17;373(6561):1372-1377.
Zhang B, Gollapudi D, Gorman J, O'Dell S, Damron LF, McKee K, Asokan M, Yang ES, Pegu A, Lin BC, Chao CW, Chen X, Gama L, Ivleva VB, Law WH, Liu C, Louder MK, Schmidt SD, Shen CH, Shi W, Stein JA, Seaman MS, McDermott AB, Carlton K, Mascola JR, Kwong PD, Lei QP, Doria-Rose NA. Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life. Sci Rep. 2022 Oct 25;12(1):17876.
Research Group
The Antibody Immunity Section discovers and studies neutralizing antibodies for HIV and other viruses and leverages the findings for vaccine design.
