tetano
Editor, Senior Moderator
The Lancet Infectious Diseases, Volume 12, Issue 10, Page 744, October 2012
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doi:10.1016/S1473-3099(12)70199-8
Pre-existing immunity in human challenge studies of influenza transmission
Julian W Tang
I was encouraged to read the Personal View by Ben Killingley and colleagues1 regarding the use of human challenge studies for the investigation of influenza transmission. Despite the often cited studies with guineapigs and ferrets, these volunteer challenge studies have far greater relevance to the transmission of influenza between people.
Killingley and colleagues1 summarise the benefits and problems of undertaking and interpreting the results of such studies comprehensively, but do not go into great detail about the potential confounding effects of pre-existing, heterologous (cross-reacting) immunity in their volunteers, which could affect several variables of interest, such as host viral shedding (load and duration), typical viral loads produced in exhaled aerosols, and the infectious doses that cause symptomatic disease.
With each influenza pandemic, the previous influenza A subtype is eventually replaced by the subsequent pandemic subtypes.2 Early work by Schild and colleagues3 recognised this occurrence and suggested that “immunological ‘memory’ may exist between the surface antigens of viruses of different subtypes”. Although at that time they stated that the immunological role of one of the other viral antigens, the membrane protein, was unknown, this particular antigen has become one of the targets for the development of a universal influenza vaccine,4 because it is more conserved than either of the other surface proteins—haemagglutinin or neuraminidase. The presence of such conserved antigens that produce a more universal immunity across different influenza A subtypes could affect the immunological make-up of human volunteers enrolled into these challenge studies and introduce a potential confounder that might be difficult to control. Yet, such antigens are known to be undetectable with standard serological assays.5
One practical way to overcome such problems is to develop immunological assays able to more fully characterise the immunological profile of each volunteer enrolled, with respect to each of the viral antigens present in the influenza A subtypes under investigation. Without such profiling, the results of human challenge studies might still be open to interpretation.
I would be interested to know how Killingley and colleagues' group plan to deal with this problem, should they take such human challenge studies forward. A well planned and executed study will be invaluable in the present climate where vast resources are now allocated to preventing, controlling, and treating influenza infection and its related complications.
I declare that I have no conflicts of interest.
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(12)70199-8/fulltext?rss=yes
<Previous Article|Next Article>
doi:10.1016/S1473-3099(12)70199-8
Pre-existing immunity in human challenge studies of influenza transmission
Julian W Tang
I was encouraged to read the Personal View by Ben Killingley and colleagues1 regarding the use of human challenge studies for the investigation of influenza transmission. Despite the often cited studies with guineapigs and ferrets, these volunteer challenge studies have far greater relevance to the transmission of influenza between people.
Killingley and colleagues1 summarise the benefits and problems of undertaking and interpreting the results of such studies comprehensively, but do not go into great detail about the potential confounding effects of pre-existing, heterologous (cross-reacting) immunity in their volunteers, which could affect several variables of interest, such as host viral shedding (load and duration), typical viral loads produced in exhaled aerosols, and the infectious doses that cause symptomatic disease.
With each influenza pandemic, the previous influenza A subtype is eventually replaced by the subsequent pandemic subtypes.2 Early work by Schild and colleagues3 recognised this occurrence and suggested that “immunological ‘memory’ may exist between the surface antigens of viruses of different subtypes”. Although at that time they stated that the immunological role of one of the other viral antigens, the membrane protein, was unknown, this particular antigen has become one of the targets for the development of a universal influenza vaccine,4 because it is more conserved than either of the other surface proteins—haemagglutinin or neuraminidase. The presence of such conserved antigens that produce a more universal immunity across different influenza A subtypes could affect the immunological make-up of human volunteers enrolled into these challenge studies and introduce a potential confounder that might be difficult to control. Yet, such antigens are known to be undetectable with standard serological assays.5
One practical way to overcome such problems is to develop immunological assays able to more fully characterise the immunological profile of each volunteer enrolled, with respect to each of the viral antigens present in the influenza A subtypes under investigation. Without such profiling, the results of human challenge studies might still be open to interpretation.
I would be interested to know how Killingley and colleagues' group plan to deal with this problem, should they take such human challenge studies forward. A well planned and executed study will be invaluable in the present climate where vast resources are now allocated to preventing, controlling, and treating influenza infection and its related complications.
I declare that I have no conflicts of interest.
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(12)70199-8/fulltext?rss=yes