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Acquired heterosubtypic antibodies in human immunity for avian H5N1 influenza.

Lynch GW, Selleck P, Sullivan JS - J Mol Genet Med (2009)

Bottom Line: These define influenza subtypes and vaccines modelled upon their HA and NA antigens provide seasonal neutralizing antibody protection against subsequent exposure to the strain and its close relatives, but give little if any protection against antigenically drifted or shifted strains.Although, such responses are of lower individual amplitudes than seasonal mechanisms they are active across influenza subtypes, and may give pre-emptive protection against new strains yet to emerge.Thus championed is the notion that seasoned humoral responses can through repeated exposure to sites widely conserved across different strains, cumulatively provide humans with a level of broad protection against emergent novel strains, such as H5N1, that is not afforded by seasonal humoral responses.

View Article: PubMed Central - PubMed

ABSTRACT
Well understood are the adaptive and dramatic neutralizing homosubtypic antibody responses to hypervariable, immunodominant sites of the hemagglutinin (HA) and neuraminidase (NA) of individual influenza strains. These define influenza subtypes and vaccines modelled upon their HA and NA antigens provide seasonal neutralizing antibody protection against subsequent exposure to the strain and its close relatives, but give little if any protection against antigenically drifted or shifted strains. Contrasting to this is a different form of acquired antibody response, called heterosubtypic immunity. This provides a more seasoned adaptive antibody response to immune-recessive epitopes that are highly-conserved amongst strains. Although, such responses are of lower individual amplitudes than seasonal mechanisms they are active across influenza subtypes, and may give pre-emptive protection against new strains yet to emerge. Heterosubtypic immunities have been well studied in animals, but surprisingly there is minimal evidence for this type of antibody immunity in humans. Thus championed is the notion that seasoned humoral responses can through repeated exposure to sites widely conserved across different strains, cumulatively provide humans with a level of broad protection against emergent novel strains, such as H5N1, that is not afforded by seasonal humoral responses.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the humoral and cell-mediated systems of heterosubtypic immunity for the delivery of cross-strain protection of novel influenzas, such as avian H5N1, via the targeting of cell-free virions and influenza protein expressing infected-cells. Both arms work in concert to protect against viral infection and propagation, pathogenesis and death. Shown is an overview of the respective mechanisms, the proteins they target, evidence of their cross-protective power, and avenues for the development of heterosubtypic-based vaccine and antiviral interventions for broad based influenza protection. [References: Jameson et al, 1999; Tumpey et al, 2001; Kong et al, 2006; Luke et al, 2006; Ichinohe et al, 2007; Roy et al, 2007; Sandlbute et al, 2007; Simmons et al, 2007; Zhou et al, 2007; Carragher et al, 2008; Gioia et al, 2008; Kayshap et al, 2008; Kreitz et al, 2008; Lee et al, 2008; Lynch et al, 2008; Roti et al, 2008; Stelzer-Braid et al, 2008]
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Figure 1: Schematic representation of the humoral and cell-mediated systems of heterosubtypic immunity for the delivery of cross-strain protection of novel influenzas, such as avian H5N1, via the targeting of cell-free virions and influenza protein expressing infected-cells. Both arms work in concert to protect against viral infection and propagation, pathogenesis and death. Shown is an overview of the respective mechanisms, the proteins they target, evidence of their cross-protective power, and avenues for the development of heterosubtypic-based vaccine and antiviral interventions for broad based influenza protection. [References: Jameson et al, 1999; Tumpey et al, 2001; Kong et al, 2006; Luke et al, 2006; Ichinohe et al, 2007; Roy et al, 2007; Sandlbute et al, 2007; Simmons et al, 2007; Zhou et al, 2007; Carragher et al, 2008; Gioia et al, 2008; Kayshap et al, 2008; Kreitz et al, 2008; Lee et al, 2008; Lynch et al, 2008; Roti et al, 2008; Stelzer-Braid et al, 2008]

Mentions: H5N1 influenza has had a higher measured mortality than the 1918 H1N1 influenza, albeit with recovery of approximately 40% of individuals surviving infection. Epidemiologic studies indicate an age-related protection with survival of approximately 60% of individuals over the age of 40 years compared to less than 25% for individuals in the 10-20 years age group (Smallman-Raynor and Cliff, 2007). Similarly data from the 1918 H1N1 and 1957 H2N2 pandemics also indicate a greater level of protection in adults (Luk et al, 2001; Epstein, 2006), which may have reduced the impact in the adult sub-population older than 65 years to that of seasonal epidemics. While apparent protection of the elderly may result from earlier immunization of this cohort from exposure to a like virus, we believe it is equally plausible to result from a lifetime acquired heterosubtypic immunity, or even a combination of both. As seasonal antibodies provide the main correlate of homotypic neutralizing protection against influenza (Schild et al, 1975; Virelizier, 1975; Delem and Jovanovic, 1978; Kashyap et al, 2008), we now raise the question of whether seasoned, cross-reactive antibodies similarly provide a significant contribution for heterosubtypic protection. Certainly, our own findings implicate a pre-existing pool of anti-influenza antibodies in an unexposed Australian population that can protect against avian H5N1 influenza, in vitro, along with H5-hemagglutinin binding antibodies that are most prominent with adult age (Lynch et al, 2008; Stelzer-Braid et al, 2008). This is also supported by observations of cross-reactive anti-neuraminidase antibodies from unexposed humans that partially protect H5N1 infected mice (Sandbulte et al, 2007). The idea of a role for low levels of pre-existing crosstypic antibodies in some humans to protect against foreign emerging influenza strains is indeed attractive. This would be supported by the other arm of heterosubtypic immunity, namely human cross-typic cell-mediated immunity, for which there is far more substantial evidence of protection against H5N1 pathogenesis and death (Jameson et al, 1999; Kreijtz et al, 2008; Lee et al, 2008; Roti et al 2008). A general overview of the combined human cellular and humoral system arms of heterosubtypic immunity and support evidence is provided in Figure 1.


Acquired heterosubtypic antibodies in human immunity for avian H5N1 influenza.

Lynch GW, Selleck P, Sullivan JS - J Mol Genet Med (2009)

Schematic representation of the humoral and cell-mediated systems of heterosubtypic immunity for the delivery of cross-strain protection of novel influenzas, such as avian H5N1, via the targeting of cell-free virions and influenza protein expressing infected-cells. Both arms work in concert to protect against viral infection and propagation, pathogenesis and death. Shown is an overview of the respective mechanisms, the proteins they target, evidence of their cross-protective power, and avenues for the development of heterosubtypic-based vaccine and antiviral interventions for broad based influenza protection. [References: Jameson et al, 1999; Tumpey et al, 2001; Kong et al, 2006; Luke et al, 2006; Ichinohe et al, 2007; Roy et al, 2007; Sandlbute et al, 2007; Simmons et al, 2007; Zhou et al, 2007; Carragher et al, 2008; Gioia et al, 2008; Kayshap et al, 2008; Kreitz et al, 2008; Lee et al, 2008; Lynch et al, 2008; Roti et al, 2008; Stelzer-Braid et al, 2008]
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2805841&req=5

Figure 1: Schematic representation of the humoral and cell-mediated systems of heterosubtypic immunity for the delivery of cross-strain protection of novel influenzas, such as avian H5N1, via the targeting of cell-free virions and influenza protein expressing infected-cells. Both arms work in concert to protect against viral infection and propagation, pathogenesis and death. Shown is an overview of the respective mechanisms, the proteins they target, evidence of their cross-protective power, and avenues for the development of heterosubtypic-based vaccine and antiviral interventions for broad based influenza protection. [References: Jameson et al, 1999; Tumpey et al, 2001; Kong et al, 2006; Luke et al, 2006; Ichinohe et al, 2007; Roy et al, 2007; Sandlbute et al, 2007; Simmons et al, 2007; Zhou et al, 2007; Carragher et al, 2008; Gioia et al, 2008; Kayshap et al, 2008; Kreitz et al, 2008; Lee et al, 2008; Lynch et al, 2008; Roti et al, 2008; Stelzer-Braid et al, 2008]
Mentions: H5N1 influenza has had a higher measured mortality than the 1918 H1N1 influenza, albeit with recovery of approximately 40% of individuals surviving infection. Epidemiologic studies indicate an age-related protection with survival of approximately 60% of individuals over the age of 40 years compared to less than 25% for individuals in the 10-20 years age group (Smallman-Raynor and Cliff, 2007). Similarly data from the 1918 H1N1 and 1957 H2N2 pandemics also indicate a greater level of protection in adults (Luk et al, 2001; Epstein, 2006), which may have reduced the impact in the adult sub-population older than 65 years to that of seasonal epidemics. While apparent protection of the elderly may result from earlier immunization of this cohort from exposure to a like virus, we believe it is equally plausible to result from a lifetime acquired heterosubtypic immunity, or even a combination of both. As seasonal antibodies provide the main correlate of homotypic neutralizing protection against influenza (Schild et al, 1975; Virelizier, 1975; Delem and Jovanovic, 1978; Kashyap et al, 2008), we now raise the question of whether seasoned, cross-reactive antibodies similarly provide a significant contribution for heterosubtypic protection. Certainly, our own findings implicate a pre-existing pool of anti-influenza antibodies in an unexposed Australian population that can protect against avian H5N1 influenza, in vitro, along with H5-hemagglutinin binding antibodies that are most prominent with adult age (Lynch et al, 2008; Stelzer-Braid et al, 2008). This is also supported by observations of cross-reactive anti-neuraminidase antibodies from unexposed humans that partially protect H5N1 infected mice (Sandbulte et al, 2007). The idea of a role for low levels of pre-existing crosstypic antibodies in some humans to protect against foreign emerging influenza strains is indeed attractive. This would be supported by the other arm of heterosubtypic immunity, namely human cross-typic cell-mediated immunity, for which there is far more substantial evidence of protection against H5N1 pathogenesis and death (Jameson et al, 1999; Kreijtz et al, 2008; Lee et al, 2008; Roti et al 2008). A general overview of the combined human cellular and humoral system arms of heterosubtypic immunity and support evidence is provided in Figure 1.

Bottom Line: These define influenza subtypes and vaccines modelled upon their HA and NA antigens provide seasonal neutralizing antibody protection against subsequent exposure to the strain and its close relatives, but give little if any protection against antigenically drifted or shifted strains.Although, such responses are of lower individual amplitudes than seasonal mechanisms they are active across influenza subtypes, and may give pre-emptive protection against new strains yet to emerge.Thus championed is the notion that seasoned humoral responses can through repeated exposure to sites widely conserved across different strains, cumulatively provide humans with a level of broad protection against emergent novel strains, such as H5N1, that is not afforded by seasonal humoral responses.

View Article: PubMed Central - PubMed

ABSTRACT
Well understood are the adaptive and dramatic neutralizing homosubtypic antibody responses to hypervariable, immunodominant sites of the hemagglutinin (HA) and neuraminidase (NA) of individual influenza strains. These define influenza subtypes and vaccines modelled upon their HA and NA antigens provide seasonal neutralizing antibody protection against subsequent exposure to the strain and its close relatives, but give little if any protection against antigenically drifted or shifted strains. Contrasting to this is a different form of acquired antibody response, called heterosubtypic immunity. This provides a more seasoned adaptive antibody response to immune-recessive epitopes that are highly-conserved amongst strains. Although, such responses are of lower individual amplitudes than seasonal mechanisms they are active across influenza subtypes, and may give pre-emptive protection against new strains yet to emerge. Heterosubtypic immunities have been well studied in animals, but surprisingly there is minimal evidence for this type of antibody immunity in humans. Thus championed is the notion that seasoned humoral responses can through repeated exposure to sites widely conserved across different strains, cumulatively provide humans with a level of broad protection against emergent novel strains, such as H5N1, that is not afforded by seasonal humoral responses.

No MeSH data available.


Related in: MedlinePlus