Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae

Christiane Abou-Zeid; Marie Pierre Gares; Jacqueline Inwald; Riny Janssen; Ying Zhang; Douglas B. Young; Charlotte Hetzel; Jonathan R. Lamb; Susan L. Baldwin; Ian M. Orme; Vladimir Yeremeev; Boris V. Nikonenko; Alexander S. Apt

doi:10.1128/iai.65.5.1856-1862.1997

Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae

Christiane Abou-Zeid, Marie Pierre Gares, Jacqueline Inwald, Riny Janssen, Ying Zhang, Douglas B. Young, Charlotte Hetzel, Jonathan R. Lamb, Susan L. Baldwin, Ian M. Orme, Vladimir Yeremeev, Boris V. Nikonenko, Alexander S. Apt

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110 Scopus citations

Abstract

A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-γ) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-γ. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.

Original language	English (US)
Pages (from-to)	1856-1862
Number of pages	7
Journal	Infection and immunity
Volume	65
Issue number	5
DOIs	https://doi.org/10.1128/iai.65.5.1856-1862.1997
State	Published - 1997
Externally published	Yes

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Infectious Diseases

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10.1128/iai.65.5.1856-1862.1997

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Abou-Zeid, C., Gares, M. P., Inwald, J., Janssen, R., Zhang, Y., Young, D. B., Hetzel, C., Lamb, J. R., Baldwin, S. L., Orme, I. M., Yeremeev, V., Nikonenko, B. V., & Apt, A. S. (1997). Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae. Infection and immunity, 65(5), 1856-1862. https://doi.org/10.1128/iai.65.5.1856-1862.1997

Abou-Zeid, C, Gares, MP, Inwald, J, Janssen, R, Zhang, Y, Young, DB, Hetzel, C, Lamb, JR, Baldwin, SL, Orme, IM, Yeremeev, V, Nikonenko, BV & Apt, AS 1997, 'Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae', Infection and immunity, vol. 65, no. 5, pp. 1856-1862. https://doi.org/10.1128/iai.65.5.1856-1862.1997

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title = "Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae",

abstract = "A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-γ) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-γ. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.",

author = "Christiane Abou-Zeid and Gares, {Marie Pierre} and Jacqueline Inwald and Riny Janssen and Ying Zhang and Young, {Douglas B.} and Charlotte Hetzel and Lamb, {Jonathan R.} and Baldwin, {Susan L.} and Orme, {Ian M.} and Vladimir Yeremeev and Nikonenko, {Boris V.} and Apt, {Alexander S.}",

year = "1997",

doi = "10.1128/iai.65.5.1856-1862.1997",

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AU - Abou-Zeid, Christiane

AU - Gares, Marie Pierre

AU - Inwald, Jacqueline

AU - Janssen, Riny

AU - Zhang, Ying

AU - Young, Douglas B.

AU - Hetzel, Charlotte

AU - Lamb, Jonathan R.

AU - Baldwin, Susan L.

AU - Orme, Ian M.

AU - Yeremeev, Vladimir

AU - Nikonenko, Boris V.

AU - Apt, Alexander S.

PY - 1997

Y1 - 1997

N2 - A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-γ) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-γ. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.

AB - A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-γ) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-γ. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.

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Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae

Abstract

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