mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies-Reference-Cited by-同舟云学术

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies

Published:2024-05-17 Issue:6697 Volume:384 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Xie Zhenfei¹^ORCID,Lin Ying-Cing¹^ORCID,Steichen Jon M.²³⁴^ORCID,Ozorowski Gabriel³⁴⁵^ORCID,Kratochvil Sven¹^ORCID,Ray Rashmi¹^ORCID,Torres Jonathan L.⁵^ORCID,Liguori Alessia²³⁴^ORCID,Kalyuzhniy Oleksandr²³⁴^ORCID,Wang Xuesong¹^ORCID,Warner John E.¹,Weldon Stephanie R.¹^ORCID,Dale Gordon A.¹^ORCID,Kirsch Kathrin H.¹,Nair Usha¹^ORCID,Baboo Sabyasachi⁶^ORCID,Georgeson Erik²³⁴^ORCID,Adachi Yumiko²³⁴^ORCID,Kubitz Michael²³⁴,Jackson Abigail M.⁵^ORCID,Richey Sara T.⁵,Volk Reid M.⁵,Lee Jeong Hyun²³⁴⁵^ORCID,Diedrich Jolene K.⁶^ORCID,Prum Thavaleak¹^ORCID,Falcone Samantha⁷,Himansu Sunny⁷^ORCID,Carfi Andrea⁷,Yates John R.⁶^ORCID,Paulson James C.²⁴⁶^ORCID,Sok Devin²³⁴^ORCID,Ward Andrew B.³⁴⁵^ORCID,Schief William R.¹²³⁴⁷^ORCID,Batista Facundo D.¹⁸^ORCID

Affiliation:

1. The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.

2. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

3. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.

4. Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.

5. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

6. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

7. Moderna Inc., Cambridge, MA 02139, USA.

8. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody–induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan–targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adk0582

Reference101 articles.

1. Broadly Neutralizing Antibodies Present New Prospects to Counter Highly Antigenically Diverse Viruses

2. Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs

3. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors

4. Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies

5. Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary-Specific Antibodies That Effectively Neutralize HIV-1

Cited by 6 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Advancing Human Vaccine Development Using Humanized Mouse Models;Vaccines;2024-09-04

2. mRNA vaccines in tumor targeted therapy: mechanism, clinical application, and development trends;Biomarker Research;2024-08-31

3. Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1;Journal of Biomedical Science;2024-08-21

4. Recent Advancements in mRNA Vaccines: From Target Selection to Delivery Systems;Vaccines;2024-08-01

5. Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates;Science;2024-05-17