Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes

Abstract

Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.

Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models. A Review

“…Initiation of apoptosis (6,17) Complement activation (8)(9)(10)18) FcR-mediated phagocytosis (10,19) Neutralization of infective agents (6,18,20,21) Adjuvanting properties (14,22) Maturation of dendritic cells (15,16) Clearance of senescent/necrotic cells (23,24) Prevention of autoimmunity (17,(25)(26)(27)(28) Opsonization of antigens (11) Enhancement of antigenicity (12) Antigen targeting to lymph nodes (13,18) T cell proliferation (29) Allograft rejection (30) cells might also mitigate the development of autoimmune diseases (17,25). On the other hand, NAb are indicated in the pathogenesis of autoimmunity, inflammatory bowel diseases, contact hypersensitivity, and sepsis (31), but only a minority of NAb and NAAb have pathogenic features (29).…”

“…Moreover, many individuals possess antibodies directed against common epitopes in highly mutating viral infections, like influenza and HIV. These, so-called "broadly neutralizing antibodies" share some characteristics with NAb (20,21). Antibodies binding previous versions of the viral strain consist of about 0.01% of the antibodies raised after infection or vaccination and react with all variants of the virus and thus appear to be multi-specific.…”

Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection

“…In anticipation of administering these antibodies in vivo , we confirmed that none bound to permeabilized HEp-2 cells ( Fig. 3f ), a common assessment of autoreactivity 28,29 .…”

Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses

“…To assess cell division of target B cells in vivo at early time points, an excess of naive 3BNC60 SI B cells (>2 × 10 6 ) were labeled with CellTrace Violet (CTV) and transferred into wild-type congenic recipient mice. The mice were injected with a control anti-idiotypic antibody (ib5; Bancroft et al, 2019) in Ribi adjuvant, or with iv8 in Ribi adjuvant, or with a multimeric nanoparticle in which the iv8 fragment antigen binding (Fab) was fused to the N-terminus of a multimerization domain derived from the Gallus gallus complement component 4B (C4b) binding protein with or without Ribi adjuvant (Hofmeyer et al, 2013). 5 d after injection, there was no detectable cell division of 3BNC60 SI B cells in mice that received the negative control antibody ib5.…”