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Comprehensive Epitope Mapping of the Epstein-Barr Virus Latent Membrane Protein-2 in Ethnically Diverse Populations

18 Years
Not Enrolling
Epstein-Barr Virus Infections

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Trial Information

Comprehensive Epitope Mapping of the Epstein-Barr Virus Latent Membrane Protein-2 in Ethnically Diverse Populations

Epstein Barr virus (EBV) can induce in immune compromised patients fatal lymphoproliferative
lesions that regress upon reversion of immune suppression or adoptive transfer of
EBV-specific CD8+ T cells. EBV can also induce neoplastic lesions in immune competent hosts
including Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal cancer (NPC).
EBV-specific CD8+ T cell responses can occur in patients with these cancers that are
qualitatively similar but quantitatively diminished compared to EBV-primed normal
individuals. Although these cancers share several features, they are characterized by
divergent patterns of expression of EBV proteins. In particular, NPC expresses
preferentially the latent membrane protein (LMP) 2 with or without expression of LMP 1 and
intermediate expression of the Epstein-Barr nuclear antigen. Thus, there is interest to
develop LMP 2-directed immunizations for patients with NPC with the hope that enhancement of
the insufficient natural immunity may lead to tumor regression. Since, the incidence of NPC
is tightly associated with ethnic background (principally Southern Chinese) and Human
Leukocyte Antigen (HLA) phenotype, diverse populations may display distinct reactivity
patterns toward EBV epitopes that may in turn be responsible for their respective
predisposition to acquire NPC. Although, several LMP 2 epitopes have been described, to our
knowledge, no systematic mapping across diverse ethnicity complemented with high-resolution
HLA typing has ever been done. We, therefore, propose to map immune dominant epitopes of
LMP 2 in EBV primed normal individuals of Caucasian or Asian (Chinese) ethnicity by
measuring interferon (IFN)-gamma transcript levels in circulating lymphocytes exposed to a
library of overlapping nonamer peptides encompassing the full sequence of LMP 2. High
resolution, sequence-based HLA typing will complement the study.

Inclusion Criteria


Normal volunteers, age greater than or equal to 18 years of Caucasian or Chinese ancestry
will be eligible for the study. Chinese ancestry will be defined as being born in China
(including Taiwan, Hong Kong and Singapore) or being first generation offspring of parents
born in China (including Taiwan, Hong Kong and Singapore).

ECOG performance status of 0 or 1.

Individuals must weigh at least 110 pounds.

Potential participants must pass the criteria for blood donors established by the American
Association of Blood Banks according to the routine screening performed within the
Department of Transfusion Medicine.

Potential participants should pass a brief physical exam to exclude potential cardiac

WBC 3000/mm(3) or greater.

Platelet count 90,000 mm(3) or greater.

Negative pregnancy test

Ante-cubital veins compatible with the apheresis process. Apheresis center nurses will
assess the ante-cubital veins of all subjects prior to enrollment. If their veins are
judged to be too small to support the intravenous catheter required for the procedure,
they will be excluded. If at the time of each apheresis procedure the nurses are unable
to obtain adequate ante-cubital vein access, the subject will be excluded.

Evidence of previous exposure to EBV infection will not represent inclusion criteria.


Potential participants will be excluded:

Who are undergoing or have undergone in the past 3 weeks any form of systemic therapy that
may affect immune function.

Who have active systemic infections, autoimmune disease or any known immunodeficiency

Who require systemic steroid therapy.

Who are pregnant.

Who are positive for hepatitis B (s)AG or HIV antibody (because of possible immune effects
of these conditions). HIV testing will be performed prior to enrollment.

Who have any form of active primary or secondary immune deficiency.

Type of Study:


Study Design:



United States: Federal Government

Study ID:




Start Date:

October 2003

Completion Date:

April 2008

Related Keywords:

  • Epstein-Barr Virus Infections
  • Nasopharyngeal Cancer
  • EBV Virus
  • Epitope Mapping
  • Epstein-Barr Virus
  • Latent Protein-2
  • Healthy Volunteer
  • HV
  • Virus Diseases
  • Epstein-Barr Virus Infections



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892