Lessons from Viral Superinfections for HIV-1 Vaccine Design

Stephanie Jost

doi:10.4172/2155-6113.s3-005

Abstract

Superinfection refers to a second viral infection in the context of a pre-existing adaptive immune response to prior infection with a viral strain that has not been cleared, the two viruses being genetically distinct yet belonging to the same genus. As such, this phenomenon provides unique settings to gain insights into the immune correlates of protection against HIV-1. The focus of this review is to discuss the current knowledge about immune responses to HIV-1 and to other viruses that are associated with partial or complete immunity to superinfection, or lack thereof, and how that could be applied to future HIV-1 vaccine strategies

Highlights

The human immunodeficiency virus type 1 (HIV-1) affects 34 million adults and children worldwide, and the ongoing spread of the epidemic resulted in about 2.5 million new infections and 1.7 million deaths in 2011 alone [1]
The current knowledge about HIV-1 superinfection discussed in this review probably does not reflect the true incidence and clinical consequences of HIV-1 superinfection
It appears that immune responses developed against a specific HIV-1 strain do not necessarily provide protection against a second infection with a genetically distinct HIV-1 strain, while a significant amount of unsuccessful or controlled HIV-1 superinfections might remain undetected

Summary

Introduction

The human immunodeficiency virus type 1 (HIV-1) affects 34 million adults and children worldwide, and the ongoing spread of the epidemic resulted in about 2.5 million new infections and 1.7 million deaths in 2011 alone [1]. Repeated exposure of HIV-1-infected individuals to the virus, or to a potential therapeutic HIV-1 vaccine, might trigger a skewing of the humoral response, leading to the generation of NAbs that might prevent new HIV-1 strains to establish a superinfection, but are not able to efficiently recognize the already present quasi species Beyond their neutralization function, which involves their variable domain, antibodies have the ability to recruit innate effectors cells that express Fcγ receptors via their constant domain, triggering various antiviral mechanisms depending on the type of cells and receptors engaged [49]. Studies report an overall poor control of the superinfecting virus, which is in most cases associated with a sudden increase in viral load and accelerated disease progression [9-11,26,2834,42,60,66,67] While this could be attributed to a loss of immunemediated control due to a lack of overlap in crucial epitopes between the two HIV-1 strains, it has been suggested that superinfection preferentially occurs in individuals initially infected with HIV-1 strains displaying a reduced fitness compared to the superinfecting virus [68]. Data accumulated far strongly suggest that protective immune responses can be mounted against HCV, and that development of a vaccine providing protection from HCV infection or promoting HCV clearance in naïve individuals might be possible

Conclusions

Findings

HIV Sequence Database Web Site