Costimulatory protein B7-1 enhances the cytotoxic T cell response and antibody response to hepatitis B surface antigen

Xiaosong He, Huo Sheng Chen, Keting Chu, Marianne Rivkina, William S. Robinson

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

There is a need for more effective therapy for chronic virus infections. A principle natural mechanism for elimination of virus-infected host cells is activation of viral antigen-specific cytotoxic T lymphocytes (CTL). In an effort to develop methods of inducing virus-specific CTL responses that might be utilized in therapy of virus infections, we have investigated the effect of B7, a costimulatory factor for T-cell activation. In this study we show that delivery of genes encoding human B7-1 and a viral antigen in the same recombinant vital vector to cells of mice induces a greater viral antigen- specific CTL response than does similar delivery of the vital antigen gene alone. Two recombinant adenovirus vectors were constructed with the foreign genes inserted in the early region 3. One of them (Ad1312) directed expression of the surface antigen gene of hepatitis B virus (HBS); the other (Ad1310) directed coexpression of HBS and human B7-1 (CD80) by means of an internal ribosomal entry site placed between the two coding sequences. When inoculated into BALB/c mice, both vectors induced a viral surface antigen- specific CTL response. The response induced by Ad1310 was stronger than that by Ad1312 as measured by a chromium release assay for CTL activity and limiting dilution analysis for CTL precursor frequency, indicating that the B7-1 gene co-delivered with the HBS gene had an enhancing effect on the CTL response against surface antigen. Ad1310 also induced a higher titer of antibody against surface antigen than did Ad1312. This result suggests that expression of a costimulatory protein and a viral antigen in the same cells in vivo induces stronger immune responses than expression of the antigen alone. This could be a novel strategy for development of both preventive and therapeutic vaccines against infectious agents.

Original languageEnglish (US)
Pages (from-to)7274-7278
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number14
DOIs
StatePublished - Jul 9 1996
Externally publishedYes

Fingerprint

Cytotoxic T-Lymphocytes
Hepatitis B Surface Antigens
Antibody Formation
Viral Antigens
T-Lymphocytes
Surface Antigens
Hepatitis B virus
Proteins
Genes
Virus Diseases
Viruses
TCF Transcription Factors
Histocompatibility Antigens Class II
Chromium
Adenoviridae
Therapeutics
Vaccines
Antigens
Antibodies

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Costimulatory protein B7-1 enhances the cytotoxic T cell response and antibody response to hepatitis B surface antigen. / He, Xiaosong; Chen, Huo Sheng; Chu, Keting; Rivkina, Marianne; Robinson, William S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 14, 09.07.1996, p. 7274-7278.

Research output: Contribution to journalArticle

He, Xiaosong ; Chen, Huo Sheng ; Chu, Keting ; Rivkina, Marianne ; Robinson, William S. / Costimulatory protein B7-1 enhances the cytotoxic T cell response and antibody response to hepatitis B surface antigen. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 14. pp. 7274-7278.
@article{b7226c5e3cd74caaa2f6469e6e582309,
title = "Costimulatory protein B7-1 enhances the cytotoxic T cell response and antibody response to hepatitis B surface antigen",
abstract = "There is a need for more effective therapy for chronic virus infections. A principle natural mechanism for elimination of virus-infected host cells is activation of viral antigen-specific cytotoxic T lymphocytes (CTL). In an effort to develop methods of inducing virus-specific CTL responses that might be utilized in therapy of virus infections, we have investigated the effect of B7, a costimulatory factor for T-cell activation. In this study we show that delivery of genes encoding human B7-1 and a viral antigen in the same recombinant vital vector to cells of mice induces a greater viral antigen- specific CTL response than does similar delivery of the vital antigen gene alone. Two recombinant adenovirus vectors were constructed with the foreign genes inserted in the early region 3. One of them (Ad1312) directed expression of the surface antigen gene of hepatitis B virus (HBS); the other (Ad1310) directed coexpression of HBS and human B7-1 (CD80) by means of an internal ribosomal entry site placed between the two coding sequences. When inoculated into BALB/c mice, both vectors induced a viral surface antigen- specific CTL response. The response induced by Ad1310 was stronger than that by Ad1312 as measured by a chromium release assay for CTL activity and limiting dilution analysis for CTL precursor frequency, indicating that the B7-1 gene co-delivered with the HBS gene had an enhancing effect on the CTL response against surface antigen. Ad1310 also induced a higher titer of antibody against surface antigen than did Ad1312. This result suggests that expression of a costimulatory protein and a viral antigen in the same cells in vivo induces stronger immune responses than expression of the antigen alone. This could be a novel strategy for development of both preventive and therapeutic vaccines against infectious agents.",
author = "Xiaosong He and Chen, {Huo Sheng} and Keting Chu and Marianne Rivkina and Robinson, {William S.}",
year = "1996",
month = "7",
day = "9",
doi = "10.1073/pnas.93.14.7274",
language = "English (US)",
volume = "93",
pages = "7274--7278",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14",

}

TY - JOUR

T1 - Costimulatory protein B7-1 enhances the cytotoxic T cell response and antibody response to hepatitis B surface antigen

AU - He, Xiaosong

AU - Chen, Huo Sheng

AU - Chu, Keting

AU - Rivkina, Marianne

AU - Robinson, William S.

PY - 1996/7/9

Y1 - 1996/7/9

N2 - There is a need for more effective therapy for chronic virus infections. A principle natural mechanism for elimination of virus-infected host cells is activation of viral antigen-specific cytotoxic T lymphocytes (CTL). In an effort to develop methods of inducing virus-specific CTL responses that might be utilized in therapy of virus infections, we have investigated the effect of B7, a costimulatory factor for T-cell activation. In this study we show that delivery of genes encoding human B7-1 and a viral antigen in the same recombinant vital vector to cells of mice induces a greater viral antigen- specific CTL response than does similar delivery of the vital antigen gene alone. Two recombinant adenovirus vectors were constructed with the foreign genes inserted in the early region 3. One of them (Ad1312) directed expression of the surface antigen gene of hepatitis B virus (HBS); the other (Ad1310) directed coexpression of HBS and human B7-1 (CD80) by means of an internal ribosomal entry site placed between the two coding sequences. When inoculated into BALB/c mice, both vectors induced a viral surface antigen- specific CTL response. The response induced by Ad1310 was stronger than that by Ad1312 as measured by a chromium release assay for CTL activity and limiting dilution analysis for CTL precursor frequency, indicating that the B7-1 gene co-delivered with the HBS gene had an enhancing effect on the CTL response against surface antigen. Ad1310 also induced a higher titer of antibody against surface antigen than did Ad1312. This result suggests that expression of a costimulatory protein and a viral antigen in the same cells in vivo induces stronger immune responses than expression of the antigen alone. This could be a novel strategy for development of both preventive and therapeutic vaccines against infectious agents.

AB - There is a need for more effective therapy for chronic virus infections. A principle natural mechanism for elimination of virus-infected host cells is activation of viral antigen-specific cytotoxic T lymphocytes (CTL). In an effort to develop methods of inducing virus-specific CTL responses that might be utilized in therapy of virus infections, we have investigated the effect of B7, a costimulatory factor for T-cell activation. In this study we show that delivery of genes encoding human B7-1 and a viral antigen in the same recombinant vital vector to cells of mice induces a greater viral antigen- specific CTL response than does similar delivery of the vital antigen gene alone. Two recombinant adenovirus vectors were constructed with the foreign genes inserted in the early region 3. One of them (Ad1312) directed expression of the surface antigen gene of hepatitis B virus (HBS); the other (Ad1310) directed coexpression of HBS and human B7-1 (CD80) by means of an internal ribosomal entry site placed between the two coding sequences. When inoculated into BALB/c mice, both vectors induced a viral surface antigen- specific CTL response. The response induced by Ad1310 was stronger than that by Ad1312 as measured by a chromium release assay for CTL activity and limiting dilution analysis for CTL precursor frequency, indicating that the B7-1 gene co-delivered with the HBS gene had an enhancing effect on the CTL response against surface antigen. Ad1310 also induced a higher titer of antibody against surface antigen than did Ad1312. This result suggests that expression of a costimulatory protein and a viral antigen in the same cells in vivo induces stronger immune responses than expression of the antigen alone. This could be a novel strategy for development of both preventive and therapeutic vaccines against infectious agents.

UR - http://www.scopus.com/inward/record.url?scp=0029957795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029957795&partnerID=8YFLogxK

U2 - 10.1073/pnas.93.14.7274

DO - 10.1073/pnas.93.14.7274

M3 - Article

C2 - 8692982

AN - SCOPUS:0029957795

VL - 93

SP - 7274

EP - 7278

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -