An Adjuvanted Herpes Simplex Virus Type 2 (HSV-2) Subunit Vaccine Elicits a T Cell Response In Mice and Is an Effective Therapeutic Vaccine In Guinea Pigs.
ABSTRACT Immunotherapeutic herpes simplex virus type 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2rTMR(340-363)) and a truncated form of infected cell polypeptide 4 (ICP4(383-766)), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells were induced in immunized mice, characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that could be recalled at least 44 days after the last immunization. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs, compared to PBS control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, it was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2- but not in GEN-003 or MM-2 vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.
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ABSTRACT: Reactivation of latent herpes simplex virus 2 (HSV-2) infections can be characterized by episodic recurrent genital lesions and/or viral shedding. We hypothesize that infected (HSV-2 pos) asymptomatic individuals have acquired T cell responses to specific HSV-2 antigen(s) that may be an important factor in controlling their recurrent disease symptoms. Our proteomic screening technology, ATLAS™, was used to characterize the antigenic repertoire of T cell responses in infected (HSV-2 pos) and virus-exposed seronegative (HSV-2 neg) subjects. T cell responses, determined by IFN-γ secretion, were generated to gL, UL2, UL11, UL21, ICP4, ICP0, ICP47 and UL40 with greater magnitude and/or frequency among cohorts of exposed HSV-2 neg or asymptomatic HSV-2 pos individuals, compared to symptomatic recurrent HSV-2 pos subjects. T cell antigens recognized preferentially among individuals who are resistant to infection or who are infected and have mild or no clinical disease may provide new targets for the design of vaccines aimed at treating and/or preventing HSV-2 infection.Virology 08/2014; 464-465. DOI:10.1016/j.virol.2014.07.018 · 3.35 Impact Factor
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ABSTRACT: Vaccines are the most cost-effective means of preventing infectious diseases and have the potential to be used in a therapeutic capacity for the treatment of numerous chronic diseases and cancer. The majority of available vaccines function by eliciting antibodies that can neutralize toxins or opsonize the pathogen leading to elimination by professional phagocytes. However, there are many infectious and non-infectious diseases for which there are no available vaccines or the current antibody-mediated vaccines offer insufficient protection. There is emerging evidence that successful protection for these conditions requires the stimulation of T cell responses in addition to antibody. Genome/proteome-wide screening of pathogens to identify appropriate antibody targets for inclusion in vaccines has become widely used in recent years. However, the application of high-throughput proteomic screening approaches to identify T cell antigens has substantially lagged behind, primarily due to the lack of methods to identify full protein targets of T cell immunity across a broad human population. In this review, we will discuss some of the significant advances that have been made in high-throughput identification of T cell antigens for the development of novel efficacious vaccines.Vaccine 06/2013; 31(37). DOI:10.1016/j.vaccine.2013.06.046 · 3.49 Impact Factor
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ABSTRACT: Genital herpes is an incurable, chronic disease that affects millions of people worldwide. Not only does genital herpes cause painful, recurrent symptoms, it is also a significant risk factor for the acquisition of other sexually transmitted infections such as HIV-1. Antiviral drugs are used to treat herpes simplex virus (HSV) infection, but they cannot stop viral shedding and transmission. Thus, developing a vaccine that can prevent or clear infection will be crucial in limiting the spread of disease. In this review we outline recent studies that improve our understanding of host responses against HSV infection, discuss past clinical vaccine trials, and highlight new strategies for vaccine design against genital herpes.Trends in Immunology 09/2013; DOI:10.1016/j.it.2013.08.001 · 12.03 Impact Factor