Daniel Lingwood

Daniel Lingwood, PhD

Principal Investigator

Core Member

Ragon Institute of Mass General, MIT, and Harvard

Associate Professor of Medicine

Harvard Medical School



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Programing vaccine antibody responses

Research Overview

The Lingwood lab studies vaccine ‘resistant’ pathogens such as influenza virus and HIV, which often trigger non-protective antibody responses. The goals of our laboratory are to define the molecular decision-making rules that the immune system uses to establish antibody targets and to apply vaccines that rework these rules to refocus antibody attention upon the conserved ‘Achilles heels’ of these viruses.

The Lingwood Lab’s research centers on defining how fundamental principles of B cell antigen recognition control epitope-targeting by the antibodies elicited by vaccines. We have described how gene-encoded antigen ‘pattern’ recognition motifs exist within the human antibody repertoire through this work. Our research centers on defining how fundamental principles of B cell antigen recognition control epitope-targeting by the antibodies elicited by vaccines. We have defined how gene-encoded antigen ‘pattern’ recognition motifs exist within the human antibody repertoire and can, within purpose-built humanized mouse systems, serve as natural substrates for refocusing humoral immunity upon ‘universal’ vaccine targets on influenza virus, HIV, and gram-negative bacteria.  We have also recently described a biological buffer system which sets the circulating level of interleukin-6 (IL-6) to regulate the output of these antibody responses and more broadly, innate immune reactions. Using a series of genetic models to manipulate the buffer-system in vivo, we now demonstrate that coordinated shifts in the buffer equilibrium regulate pro-inflammatory IL-6 signaling to enable novel anti-viral immunity at the respiratory surface.

Recognition and Media

The Lingwood Lab has been awarded a number of grants and honors in pursuit of our research. These include: NIH Director’s New Innovator Award; William F. Milton Award (Harvard University), The Gilead Research Scholars Program in HIV; and multiple R01s.


Daniel’s training has been at the interface of cell surface communication and membrane structure and function—an education that has engendered a unique perspective on solving vaccinology problems. Daniel has defined how key features of 2D molecular interactions in the membrane plane enable natural pattern recognition by human BCRs. He and his lab now demonstrate this principle serves as a natural substrate for vaccine-amplifying broadly protective anti-viral and anti-bacterial humoral responses in humanized mice.

Selected Publications

Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses

Ray R, Nait Mohamed FA, Maurer D P., Huang J, Alpay B A., Ronsard L, Xie Z, Han J, Fernandez-Quintero M, Anh Phan Q, Ursin R L., Vu M, Kirsch K H., Prum T, Rosado V C., Bracamonte-Moreno T, Okonkwo V, Bals J, McCarthy C, Nair U, Kanekiyo M, Ward A B., Schmidt A G., Batista F D., Lingwood D.

Immunity, 2024 57:1141–1159

Engaging an HIV vaccine target through the acquisition of low B cell affinity

Ronsard L., Yousif AS, Nait Mohamed FA, Feldman J, Okonkwo V, McCarthy C, Schnabel J, Caradonna T, Barnes RM, Rohrer D., Lonberg N, Schmidt A, and Lingwood D

Nature Communications, 2023 14:5249

Allelic Polymorphism Controls Autoreactivity and Vaccine-Elicitation of Human Broadly Neutralizing Antibodies Against Influenza Virus

Sangesland S, Torrents de la Peña A, Boyoglu-Barnum S, Ronsard L, Nait Mohamed FA, Bracamonte Moreno M, Barnes RM, Rohrer D, Lonberg N, Ghebremichael M, Kanekiyo M, Ward A, and Lingwood D.

Immunity, 2022 55:1693-1709

The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

Yousif AS, Ronsard R, Shah P, Omatsu T, Sangesland M, Bracamonte Moreno T, Lam EC, Vrbanac VD, Balazs AB, Reinecker H-C, and Lingwood D.

Immunity, 2021. 54:235-246

A single human VH gene allows for a broad-spectrum antibody response targeting bacterial lipopolysaccharides in the blood

Sangesland M, Yousif A, Ronsard L, Kazer SW, Zhu AL, Gatter GJ, Hayward MR, Barnes R, Quirindongo-Crespo M, Rohrer D, Lonberg N, Kwon D, Shalek AK and Lingwood D.

Cell Reports, 2020. 32:108065

Germline-encoded affinity for cognate antigen enables vaccine-amplification of a human broadly neutralizing response against influenza virus.

Sangesland M, Ronsard R, Kazer SW, Bals J, Boyoglu-Barnum S, Yousif, AS, Barnes R, Feldman J, Quirindongo-Crespo M, McTamney PM, Rohrer D, Lonberg N, Chackerian B, Graham BS, Kanekiyo M, Shalek AS, and Lingwood D. 2019.

Immunity, 2019. 51:1-15

In vitro reconstitution of B cell receptor-antigen interactions to evaluate potential vaccine candidates

Weaver GC, Villar RF, Kanekiyo M, Nabel GJ, Mascola JR, Lingwood D. 2016

Nature Protocols, 2016. 11:193-213

Structural and Genetic Basis for Development of Broadly Neutralizing Influenza Antibodies

Lingwood, D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, Wei C-J, Nabel G.

Nature, 2012. 489:566-570

Lab Team

Nathania Hartojo

Research Technician I

Faez Amokrane Nait Mohamed

Research Fellow

Thalia Bracamonte Moreno

Research Technician II

Vintus Okonkwo

Research Technologist

Larance Ronsard

Research Fellow

Daniel Tapia

Research Fellow

Rebecca Ursin

Research Fellow