Novel Nested Peptide Epitopes Recognized by CD4+ T Cells Induced by HIV-1 Conserved-Region Vaccines.

Nicola Borthwick,Tomáš Hanke,Christian Brander,Anuska Llano,Sandra Silva-Arrieta,Masafumi Takiguchi

doi:10.3390/vaccines8010028

Abstract

CD4+ T-cell responses play an important role in the immune control of the human immunodeficiency virus type 1 (HIV-1) infection and as such should be efficiently induced by vaccination. It follows that definition of HIV-1-derived peptides recognized by CD4+ T cells in association with HLA class II molecules will guide vaccine development. Here, we have characterized the fine specificity of CD4+ T cells elicited in human recipients of a candidate vaccine delivering conserved regions of HIV-1 proteins designated HIVconsv. The majority of these 19 most immunogenic regions contained novel epitopes, that is, epitopes not listed in the Los Alamos National Laboratory HIV Sequence Database, which were able in vitro to stimulate vaccinees’ CD4+ T cells to proliferate and produce interferon-γ and tumor necrosis factor-α. Accumulation of HLA class II epitopes will eventually accelerate development of HIV-1 prophylactic and therapeutic vaccines.

Highlights

There is no doubt that T cells are an important component of the host immune defense againsthuman immunodeficiency virus type 1 (HIV-1) infection [1,2]
Adaptive cellular antiviral responses are mediated by CD8+ and CD4+ T cells, which recognize foreign peptides presented by self-major histocompatibility complex molecules, in humans designated human leukocyte antigens (HLA), of class I and II, respectively
In the course of this work, we have defined novel peptides stimulatory for CD4+ T cells elicited by a candidate HIV-1 vaccine in healthy, HIV-1/2-negative volunteers in Oxford, UK

Summary

Introduction

There is no doubt that T cells are an important component of the host immune defense againstHIV-1 infection [1,2]. CD8+ cytolytic cells and B cells producing antibodies, it is well documented that CD4+ T cells can exert cytolytic activity [3,4,5,6,7]. Both CD8+ [8,9,10,11] and CD4+ [5,6,12,13,14,15,16] T-cell responses have been associated with HIV-1 immune control and their broadly specific coordinated actions are likely to be important for protection.

Methods

Results

Conclusion