Towards an HIV Vaccine Based on Immune Network Theory II

Geoffrey W Hoffmann,Heinz Kohler,Teri Otto,Michael Grant,Sybille Muller

doi:10.35248/2329-8731.19.7.190

Geoffrey W Hoffmann, Heinz Kohler + Show 3 more

Open Access

https://doi.org/10.35248/2329-8731.19.7.190

Copy DOI

Abstract

We have designed immunization protocols based on the co-section model to induce a broadening antigen antibody response against HIV1. As antigen were various antigen-antibody complexes used, including the monoclonal antibody 1F7 that is expressed on anti-HIV1 antibodies with different antigen specificities. Rabbits were used to test this concept using. Antibodies that neutralized HIV-1 of the same strain as that of the gp120 used were detected, but they did not include broadly neutralizing antibodies (BnAbs). Immunization with gp120 in adjuvant induced antibodies binding to gp120, gp41, Nef and p24, a finding predicted by the immune network theory. Furthermore a complex of 1F7 and B12 induced antibodies against gp120 and gp41, demonstrating an antigen broadening response towards achieving the goal of inducing BnAbs through immunization.

Highlights

In 1974 Jerne proposed that the immune system is organized as a network of interacting antibodies within a corresponding network of antibody-producing lymphocytes [1]
Neutralizing antibody assay Sera from bleedings of Day 42 of all the rabbits were tested for the presence of HIV-1 neutralizing antibodies by Celia Labranche of David Montefiori’s group at Duke University [14]
Rabbit 5 immunized with gp120 in ICA and CFA produced titers against gp120, and titers to gp41, p24, and nef that increase by day 42

Summary

INTRODUCTION

In 1974 Jerne proposed that the immune system is organized as a network of interacting antibodies within a corresponding network of antibody-producing lymphocytes [1]. Kohler demonstrated that the network-interaction of Ab and anti-Ab (idiotype and anti-idiotype) were symmetrical [2,3]. Richter expanded the model by suggesting that the network continues as a chain-reaction Ab1-Ab2-Ab3....[4]. Hoffmann proposed that within the cloud of Ab’s related to an immune response mutually specific clones are stimulated, a process called co-selection [5]. This phenomenon was first observed by Oudin and Casenave showing sharing of idiotopes by antibodies with different specificity [6]. This study was undertaken to 1) see if rabbits can be used to investigate the co-selection process and 2) if 1F7 can direct the response to HIV1 towards a broadly neutralizing antibodies response

MATERIALS AND METHODS

D-10-42 R10 42

DISCUSSION

CONCLUSION