IFN-γ-independent IgG2a production in mice infected with viruses and parasites

Markine-Goriaynoff, Dominique; Logt, J T van der; Truyens, Carine; Nguyễn, Tùng Lâm; Heessen, F. W. A.; Bigaignon, Geoffroy; Carlier, Yves; Coutelier, Jean‐Paul

doi:10.1093/intimm/12.2.223

Cited by 74 publications

(54 citation statements)

References 60 publications

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“…In mice, a Th1 response is associated with a predominant IgG2a antibody response and elevated IFN‐γ and other cytokines 39 , 40 . This is the typical cell‐associated response to viral infection in mice and is characterised by the recruitment of cytotoxic T cells (CTLs), natural killer cells and macrophages 41 .…”

Section: Discussionmentioning

confidence: 99%

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Svindland

Jul-Larsen

Pathirana

et al. 2011

Influenza Resp Viruses

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Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750‐2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose‐sparing strategies and an efficient mass‐vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose‐sparing potential of a chitosan‐adjuvanted intranasal H5N1 (RG‐14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)‐adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non‐adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG‐14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan‐adjuvanted SU vaccine induced an immune response superior to that of the non‐adjuvanted SU vaccine. Compared with the non‐adjuvanted SU group, the chitosan‐adjuvanted SU vaccine elicited higher numbers of influenza‐specific antibody‐secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T‐helper 1/T‐helper 2 cytokine response in the chitosan‐adjuvanted SU groups, and these groups had an increased percentage of virus‐specific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non‐adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan‐adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T‐helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFγ+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross‐clade serum reactivity, improved B‐ and T‐cell responses and dose‐sparing potential of chitosan show that a chitosan‐adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.

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Section: Discussionmentioning

confidence: 99%

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Svindland

Jul-Larsen

Pathirana

et al. 2011

Influenza Resp Viruses

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“…Therefore, it is supposed that the level of anti-VV IgG2a Ab production in T-bet Ϫ/Ϫ mice was less than that in control mice. If anti-VV IgG2a Ab is important in the clearance of VV (18), it might be possible to explain that the manner of Ab production in T-bet Ϫ/Ϫ mice is associated with the enhanced susceptibility to VV infection. In the absence of prior immunity, primary infection must generate both T-cell-mediated immunity and humoral immunity, but VV-specific T cells arise faster than anti-VV Abs.…”

Section: Ifn-␥-positive Cd8mentioning

confidence: 99%

T-bet Is Required for Protection against Vaccinia Virus Infection

Matsui

Moriya

Yoshimoto

et al. 2005

J Virol

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The transcription factor T-bet regulates the differentiation of CD4؉ T-helper type 1 (Th1) cells and represses Th2 lineage commitment. Since Th1 cells are crucial in the defense against pathogens, several studies addressed the role of T-bet in immunity to infection using T-bet knockout (T-bet ؊/؊ ) mice. Nevertheless, it is still unclear whether T-bet is required for defense. Although vaccinia virus (VV) has extensively been used as an expression vector and the smallpox vaccine, there is only limited knowledge about immunity to VV infection. The urgency to understand the immune responses has been increased because of concerns about bioterrorism. Here, we show that T-bet is critical in the defense against VV infection as follows: (i) the survival rate of T-bet ؊/؊ mice was lower than that of control littermates postinfection; (ii) T-bet ؊/؊ mice lost more weight postinfection; and (iii) control mice cleared VV faster than T-bet ؊/؊ mice. As expected, a significant Th2 shift was observed in CD4؉ T cells of T-bet ؊/؊ mice. Furthermore, absence of T-bet impaired VV-specific CD8 ؉ cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation. Cytolytic capacity of natural killer (NK) cells was also diminished in T-bet ؊/؊ mice, whereas anti-VV antibody production was not impaired. These data reveal that the enhanced susceptibility to VV infection in T-bet ؊/؊ mice was at least partially due to the Th2 shift of CD4 ؉ T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.

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“…The infectious process itself, rather than some molecular characteristics of viral antigens, is responsible for this isotypic bias of antiviral responses, possibly through the production of gamma interferon (19). Because of the functional properties of the IgG2a subclass, such as complement activation (16), binding to Fc receptors (12), and mediation of antibody-dependent cell-mediated cytotoxicity (15), it is possible that this selection of a particular isotype corresponds to the most effective response to the virus.…”

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confidence: 99%

Increased Efficacy of the Immunoglobulin G2a Subclass in Antibody-Mediated Protection against Lactate Dehydrogenase-Elevating Virus-Induced Polioencephalomyelitis Revealed with Switch Mutants

Markine-Goriaynoff

Coutelier

2002

J Virol

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Immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants were derived from an IgG3 monoclonal antibody directed against the VP3 envelope glycoprotein of lactate dehydrogenase-elevating virus (LDV). Among the four antibodies, IgG2a delayed the onset and progression of LDV-induced polioencephalomyelitis more than did the other subclasses. This suggests that the IgG2a predominance observed in many IgG antibody responses elicited by live viruses could, at least under some circumstances, correspond to the selection of the best protection for the infected host.

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IFN-γ-independent IgG2a production in mice infected with viruses and parasites

Cited by 74 publications

References 60 publications

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

T-bet Is Required for Protection against Vaccinia Virus Infection

Increased Efficacy of the Immunoglobulin G2a Subclass in Antibody-Mediated Protection against Lactate Dehydrogenase-Elevating Virus-Induced Polioencephalomyelitis Revealed with Switch Mutants

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