Current trends in negative immuno-synergy between two sexually transmitted infectious viruses: HIV-1 and HSV-1/2.
ABSTRACT In the current era of effective anti-retroviral therapy, immuno-compromised patients with HIV-1 infection do live long enough to suffer diseases caused by many opportunistic infections, such as herpes simplex virus type 1 and/or type 2 (HSV-1/2). An estimated two-third of the 40 million individuals that have contracted HIV-1 worldwide are co-infected with HSV-1/2 viruses, the causative agents of ocular oro-facial and genital herpes. The highest prevalence of HIV and HSV-1/2 infections are confined to the same regions of Sub-Saharan Africa. HSV-1/2 infections affect HIV-1 immunity, and vice versa. While important research gains have been made in understanding herpes and HIV immunity, the cellular and molecular mechanisms underlying the crosstalk between HSV-1/2 and HIV co-infection remain to be fully elucidated. Understanding the mechanisms behind the apparent HSV/HIV negative immuno-synergy maybe the key to successful HSV and HIV vaccines; both are currently unavailable. An effective herpes immunotherapeutic vaccine would in turn - indirectly - contribute in reducing HIV epidemic. The purpose of this review is: (i) to summarize the current trends in understanding the negative immuno-crosstalk between HIV and HSV-1/2 infections; and (ii) to discuss the possibility of developing a novel mucosal herpes immunotherapeutic strategy or even a combined or chimeric immunotherapeutic vaccine that simultaneously targets HIV and HSV-1/2 infections. These new trends in immunology of HSV-1/2 and HIV co-infections should become part of current efforts in preventing sexually transmitted infections. The alternative is needed to balance the ethical and financial concerns associated with the rising number of unsuccessful mono-valent clinical vaccine trials.
SourceAvailable from: Hans J Nauwynck01/2013, Degree: PhD, Supervisor: Hans Nauwynck
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ABSTRACT: Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries, their development has been difficult. During the most recent National Institute of Health (NIH) workshop titled “Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities”, basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or a whole viral protein, which contain both “pathogenic symptomatic” and “protective asymptomatic” antigens and epitopes, respectively. In this report, we continue to advocate developing “asymptomatic” epitope-based vaccine strategies that selectively incorporates “protective asymptomatic” epitopes which: (i) are exclusively recognized by effector memory CD4+ and CD8+ T cells (TEM cells) from “naturally” protected seropositive asymptomatic individuals; and (ii) protect human leukocyte antigen (HLA) transgenic animal models of ocular and genital herpes. We review the role of animal models in herpes vaccine development and discuss its current status, challenges, and prospects.Vaccine 11/2014; DOI:10.1016/j.vaccine.2014.10.002 · 3.49 Impact Factor
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ABSTRACT: Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat). In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ), induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1 infection and dissemination.PLoS ONE 07/2014; 9(7):e100844. DOI:10.1371/journal.pone.0100844 · 3.53 Impact Factor