Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers

Author:

Tokatlian Talar1,Read Benjamin J.12ORCID,Jones Christopher A.1,Kulp Daniel W.345ORCID,Menis Sergey45,Chang Jason Y. H.1ORCID,Steichen Jon M.45,Kumari Sudha1,Allen Joel D.6ORCID,Dane Eric L.1ORCID,Liguori Alessia57,Sangesland Maya8,Lingwood Daniel8,Crispin Max4567ORCID,Schief William R.4578ORCID,Irvine Darrell J.158910ORCID

Affiliation:

1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2. Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

3. Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.

4. International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.

5. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.

6. Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.

7. Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

8. The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

9. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

10. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

HIV glycans and nanoparticle vaccines Synthetic nanoparticles have attracted widespread interest for vaccine design, but how the immune system generates a response to multimeric nanoparticles remains unclear. Tokatlian et al. studied immunity generated by HIV envelope antigens arranged in either multivalent nanoparticle forms or as single monomers (see the Perspective by Wilson). The nanoparticle HIV immunogens triggered greater antibody responses compared with the monomeric forms. Glycosylation appeared key for enhanced humoral immunity because it spurred binding to mannose-binding lectin, complement fixation, and antigen trafficking to follicular dendritic cells. The findings highlight how the innate immune system recognizes HIV nanoparticles and the importance of antigen glycosylation in the design of next-generation nano-based vaccines. Science , this issue p. 649 ; see also p. 584

Funder

National Cancer Institute

National Institute of Allergy and Infectious Diseases

Ragon Institute of MGH, MIT, and Harvard

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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