Broadly Neutralizing Antibodies to Highly Antigenically Variable Viruses as Templates for Vaccine Design
Development of vaccines to highly variable viruses such as Human Immunodeficiency Virus and influenza A viruses faces multiple challenges. In this article, these challenges are described and reverse vaccinology approaches to generate universal vaccines ag
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Introduction: Broadly Neutralizing Antibodies—Challenges and Solutions...................... 1.1 Requirements for Successful Vaccines to Viral Pathogens....................................... 1.2 Highly Antigenically Variable Viruses ...................................................................... 1.3 Broadly Neutralizing Antibodies and Reverse Vaccinology..................................... 2 Broadly Neutralizing Antibodies to HIV............................................................................ 2.1 The Envelope Trimer, the Sole Target of bnAbs to HIV ......................................... 2.2 Immune-Evasive Features of the Native Env Trimer................................................ 2.3 Discovery and Isolation of bnAbs to HIV................................................................. 2.4 Major Broadly Neutralizing Epitopes on HIV Env................................................... 3 Heterosubtypic Antibodies to Influenza Virus.................................................................... 3.1 Virion Structure .......................................................................................................... 3.2 Measures of Immune Evasion (Spacing, Glycosylation, Hidden Epitopes) ............. 4 Vaccine Design Aspects for HIV and Influenza ................................................................ 4.1 Approaches for Eliciting Broadly Neutralizing/Heterosubtypic Antibodies ............. 4.2 Challenges and Approaches for the Induction of bnAbs to HIV ............................. 4.3 Challenges an Approaches for the Design of Universal Influenza Vaccines ........... 5 Conclusions.......................................................................................................................... References ..................................................................................................................................
Abstract Development of vaccines to highly variable viruses such as Human Immunodeficiency Virus and influenza A viruses faces multiple challenges. In this article, these challenges are described and reverse vaccinology approaches to generate universal vaccines against both pathogens are laid out and compared. M. G. Pauthner L. Hangartner (&) The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA e-mail: [email protected] M. G. Pauthner e-mail: [email protected] Current Topics in Microbiology and Immunology https://doi.org/10.1007/82_2020_221 © Springer Nature Switzerland AG 2020
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M. G. Pauthner and L. Hangartner
1 Introduction: Broadly Neutralizing Antibodies— Challenges and Solutions 1.1
Requirements for Successful Vaccines to Viral Pathogens
Successful vaccines to viral pathogens largely rely on the induction of functional antibody responses to effectively protect the host from infection (Plotkin 2010, 2013). While antibodies can aid host protection through a multitude of Fc-mediated functions, e.g., via antibody-dependent cellular cytotoxicity (ADCC), the most importan
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