Pia Dosenovic Project

Studies B cells for the development of new vaccines.

Research focus

B cell responses are a critical component for the protection against infections provided by vaccines. The activation of B cells is however highly regulated, to make sure the body does not mount immune responses to self-antigens, or develop un-controllable cell division, which could lead to cancer. To generate vaccines that elicit protective and long-lasting immune responses against pathogens such as HIV-1, influenza and other emerging viruses, we use genetically modified mouse models with B cells expressing human antibodies that enable us to define the trajectory and quality of antigen-specific B cells after immunization. We are also testing novel approaches for vaccine design such as using anti-idiotypic antibodies to stimulate a pathogen-specific B cell response. Collectively, our research aims to study B cell responses on the molecular and cellular levels to provide information on B cell regulation that can help develop new vaccines against HIV-1 as well as other genetically variable- and emerging pathogens.

Selected publications

Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses.
Dosenovic P, Pettersson AK, Wall A, Thientosapol ES, Feng J, Weidle C, et al
J. Exp. Med. 2019 Oct;216(10):2316-2330

Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.
Dosenovic P, Kara EE, Pettersson AK, McGuire AT, Gray M, Hartweger H, et al
Proc. Natl. Acad. Sci. U.S.A. 2018 05;115(18):4743-4748

Progress toward active or passive HIV-1 vaccination.
Escolano A, Dosenovic P, Nussenzweig MC
J. Exp. Med. 2017 01;214(1):3-16

HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies.
Steichen JM, Kulp DW, Tokatlian T, Escolano A, Dosenovic P, Stanfield RL, et al
Immunity 2016 09;45(3):483-496

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.
Escolano A, Steichen JM, Dosenovic P, Kulp DW, Golijanin J, Sok D, et al
Cell 2016 Sep;166(6):1445-1458.e12

Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice.
McGuire AT, Gray MD, Dosenovic P, Gitlin AD, Freund NT, Petersen J, et al
Nat Commun 2016 Feb;7():10618

Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice.
Dosenovic P, von Boehmer L, Escolano A, Jardine J, Freund NT, Gitlin AD, et al
Cell 2015 Jun;161(7):1505-15

Antibodies in HIV-1 vaccine development and therapy.
Klein F, Mouquet H, Dosenovic P, Scheid JF, Scharf L, Nussenzweig MC
Science 2013 Sep;341(6151):1199-204

BLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses.
Dosenovic P, Soldemo M, Scholz JL, O'Dell S, Grasset EK, Pelletier N, et al
J. Immunol. 2012 Jun;188(12):6018-26

Selective expansion of HIV-1 envelope glycoprotein-specific B cell subsets recognizing distinct structural elements following immunization.
Dosenovic P, Chakrabarti B, Soldemo M, Douagi I, Forsell MN, Li Y, et al
J. Immunol. 2009 Sep;183(5):3373-82

Funding

Current funding:

Karolinska Institutet

The Swedish Research Council (VR)

The European Research Council (ERC starting grant 2019)

Knut och Alice Wallenberg Foundation (Wallenberg Academy Fellow)

 

Previous funding:

K99 Pathway to Independence Award (NIH)

The Swedish Research Council (VR)

Karolinska Institutet