scholarly journals Immunization with Chaperone-Peptide Complex Induces Low-Avidity Cytotoxic T Lymphocytes Providing Transient Protection against Herpes Simplex Virus Infection

2002 ◽  
Vol 76 (1) ◽  
pp. 136-141 ◽  
Author(s):  
Udayasankar Kumaraguru ◽  
Malgorzata Gierynska ◽  
Shanna Norman ◽  
Barry D. Bruce ◽  
Barry T. Rouse
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
T Cell Responses ◽  
Recombinant Vaccinia Virus ◽  
T Cell Response ◽  
Peptide Epitope ◽  
Cell Responses ◽  
Simplex Virus ◽  
Shock Proteins

ABSTRACT Heat shock proteins loaded with viral peptides were shown to induce a CD8+ T cell response and confer protective immunity against challenge with herpes simplex virus (HSV). The delivery system consisted of recombinant human hsp70 coupled to the peptide SSIEFARL, which is the immunodominant peptide epitope, recognized by HSV specific T cells in C57BL/6 mice. Immunization resulted in CD8+ T-cell responses, measured by peptide-specific tetramers and peptide-induced intracellular gamma interferon expression and cytotoxicity, similar to responses resulting from immunization with a recombinant vaccinia virus that expressed SSIEFARL as a minigene (VvgB) and UV-inactivated HSV. However, the durability of the hsp70-SSIEFARL response was less than that resulting from VvgB and HSV immunization and in addition the CD8+ T-cell responses in the memory phase were functionally less effective. Mice challenged soon after immunization showed excellent immunity, but by 90 days postimmunization this had waned to be significantly less than the level of immunity in both VvgB- and HSV-immunized mice.

scholarly journals Efficacy of genital T cell responses to herpes simplex virus type 2 resulting from immunization of the nasal mucosa

Virology ◽  
2004 ◽  
Vol 318 (2) ◽  
pp. 507-515 ◽  
Author(s):  
Gregg N Milligan ◽  
Kristen L Dudley-McClain ◽  
Chin-Fun Chu ◽  
Christal G Young
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Nasal Mucosa ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
T Cell Responses ◽  
Cell Responses ◽  
Simplex Virus

scholarly journals Peripheral Blood CD4 T-Cell and Plasmacytoid Dendritic Cell (pDC) Reactivity to Herpes Simplex Virus 2 and pDC Number Do Not Correlate with the Clinical or Virologic Severity of Recurrent Genital Herpes

2012 ◽  
Vol 86 (18) ◽  
pp. 9952-9963 ◽  
Author(s):  
Nicholas J. Moss ◽  
Amalia Magaret ◽  
Kerry J. Laing ◽  
Angela Shaulov Kask ◽  
Minna Wang ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Genital Herpes ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Functional Responses ◽  
Recurrent Genital Herpes ◽  
Cell Responses ◽  
Simplex Virus

Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals.

scholarly journals Natural infection with herpes simplex virus type 1 (HSV-1) induces humoral and T cell responses to the HSV-1 glycoprotein H:L complex

2000 ◽  
Vol 81 (8) ◽  
pp. 2011-2015 ◽  
Author(s):  
Douwe F. Westra ◽  
Georges M. G. M. Verjans ◽  
Albert D. M. E. Osterhaus ◽  
Adriaan van Kooij ◽  
Gjalt W. Welling ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Herpes Simplex Virus Type ◽  
T Cell Responses ◽  
Cell Responses ◽  
Simplex Virus ◽  
Hsv 1

The glycoproteins of herpes simplex virus type 1 (HSV-1) are important targets for the immune system in the control of HSV-1 infections. The humoral and T cell responses to the glycoprotein (g)Ht(His):gL complex of HSV-1 were studied in seven HSV-1-seropositive and three HSV-1-seronegative healthy adults. In addition, responses to HSV-1 gDt were determined. As antigens, purified soluble recombinant forms of the gHt(His):gL complex produced by insect cells and of gDt produced by yeast cells were used. In contrast to seronegative donors, sera of all seropositive donors contained gHt(His): gL-specific IgG. Using peripheral blood (PB) T cells, gHt(His):gL-specific proliferative T cell responses were detected in all seropositive donors. Culture supernatants of PB T cells stimulated with recombinant gHt(His):gL contained high levels of interferon-γ and no detectable interleukin-4, indicating their Th1 phenotype. These results show that naturally acquired HSV-1 infection induces gH:gL-specific humoral and T cell responses.

scholarly journals Significant Neutralizing Antibody and Cytolytic T Cell Responses to GEN-003, a Herpes Simplex Virus Immunotherapy, in a Phase 2b Study

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S519-S519
Author(s):  
Lisa K McNeil ◽  
Amy Baccari ◽  
Veronica Clemens ◽  
David Dominguez ◽  
Tyler Fenske ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cell Responses ◽  
Simplex Virus

scholarly journals Role of CD28/CD80-86 and CD40/CD154 Costimulatory Interactions in Host Defense to Primary Herpes Simplex Virus Infection

2001 ◽  
Vol 75 (2) ◽  
pp. 612-621 ◽  
Author(s):  
Kurt H. Edelmann ◽  
Christopher B. Wilson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Systemic Infection ◽  
T Cell Responses ◽  
Cd40 Ligand ◽  
Antiviral Immune Response ◽  
Cell Responses ◽  
Simplex Virus

ABSTRACT Dependence of the primary antiviral immune response on costimulatory interactions between CD28/CD80-86 and between CD40/CD154 (CD40 ligand) has been correlated with the extent of viral replication in two models of systemic infection, lymphocytic choriomeningitis virus and vesicular stomatitis virus. To determine the role of these costimulatory interactions in the context of an acute cytolytic, but locally replicating viral infection, herpes simplex virus (HSV) infection was assessed in mice that had the CD28/CD80-86 or CD40/CD154 interactions disrupted either genetically or with blocking reagents (CTLA4Ig and MR1, respectively). CTLA4Ig treatment greatly reduced paralysis-free survival during primary acute HSV infection. This reflected an almost total ablation of the anti-HSV CD4+ and CD8+ T-cell responses due to anergy and reduced cell numbers, respectively. Disruption of CD40/CD154 interactions impaired survival, but the effect was less severe than that observed in CTLA4Ig-treated mice, with reductions observed in the CD4+T-cell but not CD8+ T-cell responses. These two costimulatory pathways functioned in part independently, since disruption of both further impaired survival. The dependence on these costimulatory interactions for the control of primary HSV infection may represent a more widespread paradigm for nonsystemic viruses, which have restricted sites of replication and which employ immunoevasive measures.

scholarly journals A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection

2019 ◽  
Vol 220 (6) ◽  
pp. 990-1000 ◽  
Author(s):  
Lesia K Dropulic ◽  
Makinna C Oestreich ◽  
Harlan L Pietz ◽  
Kerry J Laing ◽  
Sally Hunsberger ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Systemic Reactions ◽  
Simplex Virus ◽  
Double Blinded

Abstract Background Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide. Methods We conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1−/HSV2−), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2−). Sixty participants received vaccine or placebo at 0, 1, and 6 months. The primary end point was the frequency of solicited local and systemic reactions to vaccination. Results Eighty-nine percent of vaccinees experienced mild-to-moderate solicited injection site reactions, compared with 47% of placebo recipients (95% confidence interval [CI], 12.9%–67.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, −17.9% to 40.2%; P = .44). Seventy-eight percent of HSV1−/HSV2− vaccine recipients had a ≥4-fold increase in neutralizing antibody titer after 3 doses of vaccine, whereas none of the participants in the other serogroups had such responses. HSV2-specific CD4+ T-cell responses were detected in 36%, 46%, and 27% of HSV1−/HSV2−, HSV1±/HSV2+, and HSV1+/HSV2− participants, respectively, 1 month after the third dose of vaccine, and CD8+ T-cell responses were detected in 14%, 8%, and 18% of participants, respectively. Conclusions HSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees. Clinical Trials Registration NCT01915212.

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