scholarly journals An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

2013 ◽  
Vol 87 (7) ◽  
pp. 3930-3942 ◽  
Author(s):  
M. Skoberne ◽  
R. Cardin ◽  
A. Lee ◽  
A. Kazimirova ◽  
V. Zielinski ◽  
...  
1987 ◽  
Vol 165 (2) ◽  
pp. 459-470 ◽  
Author(s):  
E Watari ◽  
B Dietzschold ◽  
G Szokan ◽  
E Heber-Katz

Immunization against viral pathogens is generally directed toward the induction of virus neutralizing antibody (VNA) and the maintenance of the potential for a second-set (IgG) response. Indeed, an elevated level of specific antibody is considered a reliable clinical indicator that a state of immunity exists in the host. However, in the case of herpes simplex virus (HSV), the presence of circulating VNA does not necessarily correlate with protection. Thus, it has been found that secondary infections occur in individuals even with high neutralizing titers to HSV, suggesting that antibody to the virus may be useless or even deleterious. In consideration of these facts, we were interested in inducing a T cell response to HSV. We had already shown that synthetic peptides corresponding to the NH3-terminal region of the glycoprotein D (gD) molecule of HSV could induce a strong T cell response when injected into mice, but did not, by themselves, confer protection. In this report, we examined the ability of peptides, covalently coupled to palmitic acid and incorporated into liposomes, to induce virus-specific T cell responses that confer protection against a lethal challenge of HSV-2. We have demonstrated that long-term protective immunity is achieved with a single immunization in the absence of neutralizing antibody when antigen is presented in this form. Furthermore, T cells but not serum from such immune mice can adoptively transfer this protection.


2006 ◽  
Vol 80 (11) ◽  
pp. 5509-5515 ◽  
Author(s):  
Nancy Hosken ◽  
Patrick McGowan ◽  
Amalia Meier ◽  
David M. Koelle ◽  
Paul Sleath ◽  
...  

ABSTRACT Cytolytic T cells play a major role in controlling herpes simplex virus type 2 (HSV-2) infections in humans. In an effort to more thoroughly evaluate the response to HSV-2 directly, ex vivo, we developed an enzyme-linked immunospot (ELISPOT) assay that utilized pools of overlapping synthetic peptides presented by autologous dendritic cells to purified CD8+ T cells. Donor response rates to individual open reading frames (ORFs) ranged from fewer than 5% responding to as many as 70% responding, with the greatest frequency of responses (by ORF) being directed against UL39, UL25, UL27, ICP0, UL46, and UL47 in descending order of frequency. HSV-2-seropositive subjects responded to as few as 3 or as many as 46 of the 48 ORFs tested, with a median of 11 ORFs recognized. HLA-B*07 expression correlated with stronger responses overall that were directed primarily against UL49 and UL46. Cumulative precursor frequencies in the blood ranged from 500 to almost 6,000 HSV-2 spot-forming units/106 CD8+ T cells. The magnitude and breadth of the response in the infected population were greater than previously appreciated. Whether this variability in the CD8+ T-cell response within individuals is associated with the frequency of viral reactivation warrants further study.


1999 ◽  
Vol 73 (9) ◽  
pp. 7619-7626 ◽  
Author(s):  
Morgan E. Wallace ◽  
Rachael Keating ◽  
William R. Heath ◽  
Francis R. Carbone

ABSTRACT Many virus infections give rise to surprisingly limited T-cell responses directed to very few immunodominant determinants. We have been examining the cytotoxic T-lymphocyte (CTL) response to herpes simplex virus type 1 (HSV-1) infection. Previous studies have identified the glycoprotein B-derived peptide from residues 498 to 505 (gB498–505) as one of at least three determinants recognized by HSV-1-specific CTLs isolated from C57BL/6 mice. We had previously found that in vitro-derived CTLs directed to gB498–505 show a characteristic pattern of T-cell receptor (TCR) usage, with 60% of gB498–505-specific CD8+ T cells expressing BV10+ TCR β chains and a further 20% expressing BV8S1. In this report, we confirm that this TCR V-region bias is also reflected in the ex vivo response to HSV-1 infection. A high proportion of activated CD8+draining lymph node cells were found to express these dominant V regions, suggesting that a substantial number of in vivo responding T cells were directed to this one viral determinant. The use of an HSV-1 deletion mutant lacking the gB498–505 determinant in combination with accurate intracellular gamma interferon staining allowed us to quantify the extent of gB-specific T-cell dominance. Together, these results suggested that between 70 and 90% of all CD8+ HSV-1-specific T cells target gB498–505. While deletion of this determinant resulted in an attenuated CD8+ T-cell response, it also permitted the emergence of one or more previously unidentified cryptic specificities. Overall, HSV-1 infection of C57BL/6 mice results in an extremely focused pattern of CD8+ T-cell selection in terms of target specificity and TCR expression.


2004 ◽  
Vol 78 (23) ◽  
pp. 13082-13089 ◽  
Author(s):  
Felix N. Toka ◽  
Susmit Suvas ◽  
Barry T. Rouse

ABSTRACT It has become evident that naturally occurring CD25+ regulatory T cells (Treg cells) not only influence self-antigen specific immune response but also dampen foreign antigen specific immunity. This report extends our previous findings by demonstrating that immunity to certain herpes simplex virus (HSV) vaccines is significantly elevated and more effective if Treg cell response is curtailed during either primary or recall immunization. The data presented here show that removal of CD25+ Treg cells prior to SSIEFARL-CpG or gB-DNA immunization significantly enhanced the resultant CD8+ T-cell response to the immunodominant SSIEFARL peptide. The enhanced CD8+ T-cell reactivity in Treg cell-depleted animals was between two- and threefold and evident in both acute and memory stages. Interestingly, removal of CD25+ Treg cells during the memory recall response to plasmid immunization resulted in a twofold increase in CD8+ T-cell memory pool. Moreover, in the challenge experiments, memory CD8+ T cells generated with plasmid DNA in the absence of Treg cells cleared the virus more effectively compared with control groups. We conclude that CD25+ Treg cells quantitatively as well as qualitatively affect the memory CD8+ T-cell response generated by gB-DNA vaccination against HSV. However, it remains to be seen if all types of vaccines against HSV are similarly affected by CD25+ Treg cells and if it is possible to devise means of limiting Treg cell activity to enhance vaccine efficacy.


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