Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: the Old, the New, and the Unknown

Overview

Journal Clin Dev Immunol

Specialty Allergy & Immunology

Date 2012 May 2

PMID 22548113

Citations 40

Authors

Aziz Alami Chentoufi

Elizabeth Kritzer

David M Yu

Anthony B Nesburn

Lbachir BenMohamed

Affiliations

Soon will be listed here.

Abstract

The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally "protected" exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4(+) and CD8(+) T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation "asymptomatic" clinical herpes vaccines, and discuss future mucosal "asymptomatic" prime-boost vaccines that could optimize local protective immunity.

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References

Iwasaki A, Kelsall B . Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. J Exp Med. 1999; 190(2):229-39. PMC: 2195574. DOI: 10.1084/jem.190.2.229. View

Koelle D, Corey L . Herpes simplex: insights on pathogenesis and possible vaccines. Annu Rev Med. 2008; 59:381-95. DOI: 10.1146/annurev.med.59.061606.095540. View

Franchini M, Hefti H, Vollstedt S, Glanzmann B, Riesen M, Ackermann M . Dendritic cells from mice neonatally vaccinated with modified vaccinia virus Ankara transfer resistance against herpes simplex virus type I to naive one-week-old mice. J Immunol. 2004; 172(10):6304-12. DOI: 10.4049/jimmunol.172.10.6304. View

Thomas J, Rouse B . Immunopathogenesis of herpetic ocular disease. Immunol Res. 1997; 16(4):375-86. DOI: 10.1007/BF02786400. View

KUKLIN N, Daheshia M, Chun S, Rouse B . Role of mucosal immunity in herpes simplex virus infection. J Immunol. 1998; 160(12):5998-6003. View

Khanna K, Bonneau R, Kinchington P, Hendricks R . Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity. 2003; 18(5):593-603. PMC: 2871305. DOI: 10.1016/s1074-7613(03)00112-2. View

Prabhakaran K, Sheridan B, Kinchington P, Khanna K, Decman V, Lathrop K . Sensory neurons regulate the effector functions of CD8+ T cells in controlling HSV-1 latency ex vivo. Immunity. 2005; 23(5):515-25. DOI: 10.1016/j.immuni.2005.09.017. View

Koelle D, Corey L . Recent progress in herpes simplex virus immunobiology and vaccine research. Clin Microbiol Rev. 2003; 16(1):96-113. PMC: 145296. DOI: 10.1128/CMR.16.1.96-113.2003. View

Zhou S, Kurt-Jones E, Mandell L, Cerny A, Chan M, Golenbock D . MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection. Eur J Immunol. 2005; 35(3):822-30. DOI: 10.1002/eji.200425730. View

10.

Perng G, Maguen B, Jin L, Mott K, Kurylo J, BenMohamed L . A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5' end of the latency-associated transcript produces a protein in infected rabbits. J Virol. 2002; 76(16):8003-10. PMC: 155148. DOI: 10.1128/jvi.76.16.8003-8010.2002. View

11.

Straus S, Corey L, Burke R, Savarese B, Barnum G, Krause P . Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet. 1994; 343(8911):1460-3. DOI: 10.1016/s0140-6736(94)92581-x. View

12.

Knaup B, Schunemann S, Wolff M . Subclinical reactivation of herpes simplex virus type 1 in the oral cavity. Oral Microbiol Immunol. 2001; 15(5):281-3. DOI: 10.1034/j.1399-302x.2000.150502.x. View

13.

Dasgupta G, Chentoufi A, Nesburn A, Wechsler S, BenMohamed L . New concepts in herpes simplex virus vaccine development: notes from the battlefield. Expert Rev Vaccines. 2009; 8(8):1023-35. PMC: 2760836. DOI: 10.1586/erv.09.60. View

14.

Brandtzaeg P, Pabst R . Let's go mucosal: communication on slippery ground. Trends Immunol. 2004; 25(11):570-7. DOI: 10.1016/j.it.2004.09.005. View

15.

Dasgupta G, BenMohamed L . Of mice and not humans: how reliable are animal models for evaluation of herpes CD8(+)-T cell-epitopes-based immunotherapeutic vaccine candidates?. Vaccine. 2011; 29(35):5824-36. PMC: 3159167. DOI: 10.1016/j.vaccine.2011.06.083. View

16.

Manservigi R, Boero A, Argnani R, Caselli E, Zucchini S, Miriagou V . Immunotherapeutic activity of a recombinant combined gB-gD-gE vaccine against recurrent HSV-2 infections in a guinea pig model. Vaccine. 2004; 23(7):865-72. DOI: 10.1016/j.vaccine.2004.08.025. View

17.

Dasgupta G, Nesburn A, Wechsler S, BenMohamed L . Developing an asymptomatic mucosal herpes vaccine: the present and the future. Future Microbiol. 2009; 5(1):1-4. PMC: 4512283. DOI: 10.2217/fmb.09.101. View

18.

Gahery-Segard H, Pialoux G, Figueiredo S, Igea C, Surenaud M, Gaston J . Long-term specific immune responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine: characterization of CD8+-T-cell epitopes recognized. J Virol. 2003; 77(20):11220-31. PMC: 224965. DOI: 10.1128/jvi.77.20.11220-11231.2003. View

19.

Moyle P, Toth I . Self-adjuvanting lipopeptide vaccines. Curr Med Chem. 2008; 15(5):506-16. DOI: 10.2174/092986708783503249. View

20.

Kim S, Brehm M, Welsh R, Selin L . Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation. J Immunol. 2002; 169(1):90-8. DOI: 10.4049/jimmunol.169.1.90. View