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Cross-subtype immunity against avian influenza in persons recently vaccinated for influenza.

Gioia C, Castilletti C, Tempestilli M, Piacentini P, Bordi L, Chiappini R, Agrati C, Squarcione S, Ippolito G, Puro V, Capobianchi MR, Poccia F - Emerging Infect. Dis. (2008)

Bottom Line: Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease.No correlation between influenza-specific CD4 T cells and humoral responses was observed.N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani, Istituti di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, Rome, Italy.

ABSTRACT
Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease. The aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (H5N1) strains in healthy donors vaccinated for seasonal influenza A (H1N1)/(H3N2). A small frequency of CD4 T cells specific for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells. We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors. No correlation between influenza-specific CD4 T cells and humoral responses was observed. N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point. These findings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian influenza A virus subtype H5N1 by seasonal influenza vaccination.

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H5 versus N1 specificity of the cell-mediated response. Profiling of influenza (H5N1)–specific CD4 T-cell response in a representative study participant is shown. Peripheral blood mononuclear cells (PBMC) were expanded in vitro in the presence of interleukin-2 (IL-2) and stimulated with inactivated influenza (H5N1) virus (B), peptide pool composed by 4 peptides from H5 and N1 (C), H5 peptides (D) and N1 peptides (E). Panel A shows unstimulated cultures. Dot plots showed the presence, at similar frequency, of specific CD4 T cells when PBMC were stimulated with inactivated influenza (H5N1) virus (panel B, 1.82%), influenza (H5N1) peptides (panel C, 1.52%), and N1 peptides (panel E, 1.49%). No specific CD4 T cells producing interferon-gamma (IFN-γ) were observed after challenge with H5 peptides (D). As negative control, either mock-infected culture supernatants or irrelevant peptides were used, giving results very similar to unstimulated cultures (not shown). A similar pattern was observed in 4 other study participants, supporting the hypothesis that the actual target of cross-subtype immunity could be N1.
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Figure 2: H5 versus N1 specificity of the cell-mediated response. Profiling of influenza (H5N1)–specific CD4 T-cell response in a representative study participant is shown. Peripheral blood mononuclear cells (PBMC) were expanded in vitro in the presence of interleukin-2 (IL-2) and stimulated with inactivated influenza (H5N1) virus (B), peptide pool composed by 4 peptides from H5 and N1 (C), H5 peptides (D) and N1 peptides (E). Panel A shows unstimulated cultures. Dot plots showed the presence, at similar frequency, of specific CD4 T cells when PBMC were stimulated with inactivated influenza (H5N1) virus (panel B, 1.82%), influenza (H5N1) peptides (panel C, 1.52%), and N1 peptides (panel E, 1.49%). No specific CD4 T cells producing interferon-gamma (IFN-γ) were observed after challenge with H5 peptides (D). As negative control, either mock-infected culture supernatants or irrelevant peptides were used, giving results very similar to unstimulated cultures (not shown). A similar pattern was observed in 4 other study participants, supporting the hypothesis that the actual target of cross-subtype immunity could be N1.

Mentions: Because some study participants were reactive to inactivated influenza virus (H5N1) as well as to a peptide pool composed of 2 peptides from H5 and 2 from N1 consensus sequences, we analyzed whether this reactivity was preferentially directed against HA or NA. As shown by PBMC from a representative donor in Figure 2, the frequency of IFN-γ–producing CD4 effector T cells was appreciable after challenge with the inactivated influenza virus (H5N1) (Figure 2, panel B: 1.82% of IFN-γ+ CD4+ T cells) or with the H5/N1 peptides (Figure 2, panel C: 1.52% of IFN-γ+ CD4+ T cells). The response of PBMC from the same donor to N1 peptides was positive, whereas the response to H5 peptides was at background level (Figure 2, panel E and D: 1.49% vs. 0.14% of IFN-γ+ CD4+ T cells), a finding that suggests that N1 seems to be the main target for cell-mediated cross-type immunity against influenza (H5N1) and influenza (H3N2)/(H1N1) vaccine strains. A similar pattern was observed in 4 other study participants, which supports the hypothesis that the target of cross-subtype immunity could actually be N1.


Cross-subtype immunity against avian influenza in persons recently vaccinated for influenza.

Gioia C, Castilletti C, Tempestilli M, Piacentini P, Bordi L, Chiappini R, Agrati C, Squarcione S, Ippolito G, Puro V, Capobianchi MR, Poccia F - Emerging Infect. Dis. (2008)

H5 versus N1 specificity of the cell-mediated response. Profiling of influenza (H5N1)–specific CD4 T-cell response in a representative study participant is shown. Peripheral blood mononuclear cells (PBMC) were expanded in vitro in the presence of interleukin-2 (IL-2) and stimulated with inactivated influenza (H5N1) virus (B), peptide pool composed by 4 peptides from H5 and N1 (C), H5 peptides (D) and N1 peptides (E). Panel A shows unstimulated cultures. Dot plots showed the presence, at similar frequency, of specific CD4 T cells when PBMC were stimulated with inactivated influenza (H5N1) virus (panel B, 1.82%), influenza (H5N1) peptides (panel C, 1.52%), and N1 peptides (panel E, 1.49%). No specific CD4 T cells producing interferon-gamma (IFN-γ) were observed after challenge with H5 peptides (D). As negative control, either mock-infected culture supernatants or irrelevant peptides were used, giving results very similar to unstimulated cultures (not shown). A similar pattern was observed in 4 other study participants, supporting the hypothesis that the actual target of cross-subtype immunity could be N1.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2600140&req=5

Figure 2: H5 versus N1 specificity of the cell-mediated response. Profiling of influenza (H5N1)–specific CD4 T-cell response in a representative study participant is shown. Peripheral blood mononuclear cells (PBMC) were expanded in vitro in the presence of interleukin-2 (IL-2) and stimulated with inactivated influenza (H5N1) virus (B), peptide pool composed by 4 peptides from H5 and N1 (C), H5 peptides (D) and N1 peptides (E). Panel A shows unstimulated cultures. Dot plots showed the presence, at similar frequency, of specific CD4 T cells when PBMC were stimulated with inactivated influenza (H5N1) virus (panel B, 1.82%), influenza (H5N1) peptides (panel C, 1.52%), and N1 peptides (panel E, 1.49%). No specific CD4 T cells producing interferon-gamma (IFN-γ) were observed after challenge with H5 peptides (D). As negative control, either mock-infected culture supernatants or irrelevant peptides were used, giving results very similar to unstimulated cultures (not shown). A similar pattern was observed in 4 other study participants, supporting the hypothesis that the actual target of cross-subtype immunity could be N1.
Mentions: Because some study participants were reactive to inactivated influenza virus (H5N1) as well as to a peptide pool composed of 2 peptides from H5 and 2 from N1 consensus sequences, we analyzed whether this reactivity was preferentially directed against HA or NA. As shown by PBMC from a representative donor in Figure 2, the frequency of IFN-γ–producing CD4 effector T cells was appreciable after challenge with the inactivated influenza virus (H5N1) (Figure 2, panel B: 1.82% of IFN-γ+ CD4+ T cells) or with the H5/N1 peptides (Figure 2, panel C: 1.52% of IFN-γ+ CD4+ T cells). The response of PBMC from the same donor to N1 peptides was positive, whereas the response to H5 peptides was at background level (Figure 2, panel E and D: 1.49% vs. 0.14% of IFN-γ+ CD4+ T cells), a finding that suggests that N1 seems to be the main target for cell-mediated cross-type immunity against influenza (H5N1) and influenza (H3N2)/(H1N1) vaccine strains. A similar pattern was observed in 4 other study participants, which supports the hypothesis that the target of cross-subtype immunity could actually be N1.

Bottom Line: Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease.No correlation between influenza-specific CD4 T cells and humoral responses was observed.N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani, Istituti di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, Rome, Italy.

ABSTRACT
Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease. The aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (H5N1) strains in healthy donors vaccinated for seasonal influenza A (H1N1)/(H3N2). A small frequency of CD4 T cells specific for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells. We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors. No correlation between influenza-specific CD4 T cells and humoral responses was observed. N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point. These findings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian influenza A virus subtype H5N1 by seasonal influenza vaccination.

Show MeSH
Related in: MedlinePlus