Thursday, June 18, 2015

Study: Natural T Cell–mediated Protection against Seasonal and Pandemic Influenza



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Fair or not, influenza can produce a wide spectrum of illness, ranging from mild or even asymptomatic presentation to severe and/or life threatening disease. Although co-morbidities (COPD, Asthma, pregnancy, etc. ) can lead to a greater chance of complications, some people just naturally seen to have an easier time with the flu than do others.


Last March, in A Genetic Predisposition To Severe Flu Infection (and before that in 2012’s Luck Of The Draw) we looked at several different ways genetics might play a part in the severity and outcome of flu infection.  

Serological studies have shown that a high percentage of people who are infected with the flu either experience mild, or sub-clinical symptoms.  Last year’s Lancet: Community Burden & Severity Of Seasonal And Pandemic Influenza found over five years that as many as 75% of those who showed serological evidence of infection reported no significant influenza symptoms.


There were limitations to this study, of course, including low participation rates, no data gathered from patients < 5 years of age, self-reporting of symptoms, and difficulty in obtaining a fully representative sample.

Still . . . .


While great for those who can carry the virus asymptomatically, studies have suggested that these cases may still be able to spread the virus (see PLoS One: Influenza Viral Shedding & Asymptomatic Infections), which is one of the reasons why fever screening at airports during a pandemic is unlikely to provide much benefit.

Earlier this week a new study was published in the American Journal of Respiratory and Critical Care Medicine where researchers from University College London conducted a cohort study of more than 1,400 Brits and discovered a high percentage (43%) carried a natural T-Cell that targeted the influenza virus nucleoprotein.


Unlike antibodies (which we get from previous infections or a vaccine) - T-Cell don't prevent infection - but they can lessen the symptoms.  Those who carried these specific T-Cells still caught the flu, but generally suffered much milder symptoms . . .or no symptoms at all. 


Interestingly, the same T-Cells were effective against both H1N1 and H3N2.  It is unknown whether this `immunity’ would extend to other flu subtypes, but if the cross-reactivity is great enough, boosting broadly reactive T-cells instead of trying to match ever-changing flu strains might be the way of the future for flu vaccines.


Natural T Cell–mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study

Andrew C. Hayward1*, Lili Wang2*, Nilu Goonetilleke2,3, Ellen B. Fragaszy1,4, Alison Bermingham5, Andrew Copas6, Oliver Dukes1, Elizabeth R. C. Millett4,6, Irwin Nazareth7, Jonathan S. Nguyen-Van-Tam8, John M. Watson9, Maria Zambon5, the Flu Watch Group, Anne M. Johnson6§, and Andrew J. McMichael2§ 

Corresponding Author: Andrew C. Hayward


Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown.

Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.

Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases.

Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11–0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P  = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact.

Conclusions: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.

1 comment:

Craig vanderwagen said...

So who is working on this platform idea? The proposal has merit, but who is invested in the science of T cell modification enough to push the discovery science through advanced development? .....many to talk to about this...