A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge

Jorge Reyes Del Valle, Patricia Devaux, Gregory Hodge, Nicholas J. Wegner, Michael B. McChesney, Roberto Cattaneo

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with single-dose scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with a vaccine strain background and expression vector properties. Hepatitis B surface antigen (HBsAg) expression cassettes were inserted into this cDNA and three MVs expressing HBsAg at different levels generated. All vectored MVs, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated into rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis87), control naive monkeys showed a classic measles rash and high viral loads. In contrast, all monkeys immunized with vaccine or a control nonvectored recombinant vaccine or HBsAg-expressing vectored MV remained healthy, with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are discussed.

Original languageEnglish (US)
Pages (from-to)10597-10605
Number of pages9
JournalJournal of Virology
Volume81
Issue number19
DOIs
StatePublished - Oct 2007

Fingerprint

Measles virus
Macaca
Hepatitis B Surface Antigens
antibodies
Antibodies
vaccines
Vaccines
Hepatitis B virus
viral load
Macaca mulatta
Viral Load
humoral immunity
Haplorhini
monkeys
Complementary DNA
hepatitis B antigens
Hepatitis B Vaccines
Synthetic Vaccines
mice
Measles

ASJC Scopus subject areas

  • Immunology

Cite this

A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge. / Del Valle, Jorge Reyes; Devaux, Patricia; Hodge, Gregory; Wegner, Nicholas J.; McChesney, Michael B.; Cattaneo, Roberto.

In: Journal of Virology, Vol. 81, No. 19, 10.2007, p. 10597-10605.

Research output: Contribution to journalArticle

Del Valle, Jorge Reyes ; Devaux, Patricia ; Hodge, Gregory ; Wegner, Nicholas J. ; McChesney, Michael B. ; Cattaneo, Roberto. / A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge. In: Journal of Virology. 2007 ; Vol. 81, No. 19. pp. 10597-10605.
@article{2846493e614e48e8a19131ecf55d6894,
title = "A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge",
abstract = "Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with single-dose scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with a vaccine strain background and expression vector properties. Hepatitis B surface antigen (HBsAg) expression cassettes were inserted into this cDNA and three MVs expressing HBsAg at different levels generated. All vectored MVs, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated into rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis87), control naive monkeys showed a classic measles rash and high viral loads. In contrast, all monkeys immunized with vaccine or a control nonvectored recombinant vaccine or HBsAg-expressing vectored MV remained healthy, with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are discussed.",
author = "{Del Valle}, {Jorge Reyes} and Patricia Devaux and Gregory Hodge and Wegner, {Nicholas J.} and McChesney, {Michael B.} and Roberto Cattaneo",
year = "2007",
month = "10",
doi = "10.1128/JVI.00923-07",
language = "English (US)",
volume = "81",
pages = "10597--10605",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "19",

}

TY - JOUR

T1 - A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge

AU - Del Valle, Jorge Reyes

AU - Devaux, Patricia

AU - Hodge, Gregory

AU - Wegner, Nicholas J.

AU - McChesney, Michael B.

AU - Cattaneo, Roberto

PY - 2007/10

Y1 - 2007/10

N2 - Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with single-dose scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with a vaccine strain background and expression vector properties. Hepatitis B surface antigen (HBsAg) expression cassettes were inserted into this cDNA and three MVs expressing HBsAg at different levels generated. All vectored MVs, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated into rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis87), control naive monkeys showed a classic measles rash and high viral loads. In contrast, all monkeys immunized with vaccine or a control nonvectored recombinant vaccine or HBsAg-expressing vectored MV remained healthy, with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are discussed.

AB - Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with single-dose scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with a vaccine strain background and expression vector properties. Hepatitis B surface antigen (HBsAg) expression cassettes were inserted into this cDNA and three MVs expressing HBsAg at different levels generated. All vectored MVs, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated into rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis87), control naive monkeys showed a classic measles rash and high viral loads. In contrast, all monkeys immunized with vaccine or a control nonvectored recombinant vaccine or HBsAg-expressing vectored MV remained healthy, with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are discussed.

UR - http://www.scopus.com/inward/record.url?scp=34648833266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34648833266&partnerID=8YFLogxK

U2 - 10.1128/JVI.00923-07

DO - 10.1128/JVI.00923-07

M3 - Article

VL - 81

SP - 10597

EP - 10605

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 19

ER -