Lessons from H1N1: How Partial Immunity Can Kill You
We are now in the thick of the influenza season, and it is a true shame that the emphasis on vaccines against the flu has drowned out any mainstream discussion much less headlines for an important study recently released in Nature about the 2009 H1N1 influenza virus: Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes . The press release is worth reading.
There are a few initial things that make this study worth noting:
1) It is not funded by the industrial/governmental health care complex
2) It is short, concise, and doesn’t draw any reaching conclusions
3) It furthers our understanding of the 2009 H1N1 Flu by doing a rigorous scientific follow-up of real cases.
The last point is a refreshing change as one of the best ways to learn something is to examine the medical outcomes for real people and this is something we don’t see very often from our medical authorities. The study itself does not address vaccines but the findings have important implications for mass influenza vaccination policies.
This study is extremely short and dense. I’ll try to summarize it here for the lay person:
Who did they study?
- They looked at patients who were admitted to a hospital in Argentina suffering from H1N1
- They looked at patients who were hospitalized for non-H1N1 related influenza as controls
- They studied lung tissue from people who died in the 1957 influenza pandemic
What did they look at?
- They were trying to understand why 2009 H1N1 Influenza severely affected a small set of middle aged adults and not the elderly or young — this is different from typical influenza disease patterns
- They studied a number of immune system markers across a variety of patients who suffered a different severity of disease.
1) The viral load of 2009 H1N1 was actually lower compared to typical seasonal influenza. This result was consistent across all patients including those who died. This is consistent with the observation that the overall disease burden due to H1N1 was less than other more typical influenza seasons.
Conclusion: The 2009 H1N1 virus was not more severe or more dangerous than typical influenza on it’s own
2) The elderly had high numbers of antibodies that were protective against 2009 H1N1.
Conclusion: The elderly were protected by prior exposure to a similar virus in the distant past
3) The most severe cases of illness (mid age adults) had high levels of non-protective H1 antibodies. These anti-bodies have low avidity which means they attach to the disease antigens but they don’t attach well enough to neutralize the disease. These patients had antibodies with good avidity (meaning protective) against 1999 H1 disease.
Conclusion: Prior exposure to a similar disease (or vaccine) resulted in the formation of antibodies that could attach to the disease but were ultimately ineffective in neutralizing it
4) The most severe cases of illness had high levels of immune-complex disease markers. An “Immune Complex” is the result of the combination of antibodies bound to disease antigens. Immune Complex disease is when the immune system attacks the resulting immune complex and causes serious damage. In the cases of severe H1N1 this usually resulted in serious respiratory damage and sometimes death. Severe cases from non H1N1 influenza patients did not have the same markers.
Conclusion: Non-protective antibodies for 2009 H1N1 resulted in immune complex disease which caused the cases of severe illness.
5) Studies of lung tissue from 1957 H2 pandemic also showed markers of immune complex disease
Conclusion: Immune Complex Disease is a strong candidate for causation of influenza pandemics where the overall virus is mild, but still results in severe illness in an atypical population like mid-age adults.
In reading through some of the references, it is interesting to note that immune complex disease has been studied before, specifically in research surrounding a failed RSV vaccine from the 1960′s. The failed vaccine in the 1960′s induced immune complex disease in the children that were vaccinated, resulting in many cases of enhanced respiratory disease (ERD) including 2 deaths. Mouse model research done in the 1980′s and in 2002 clearly identified that the antibodies produced by the vaccine had low avidity and caused immune complex disease. 
This new information brings to mind a lot of questions surrounding the medical community’s policy of mass influenza vaccination.
1) Do influenza vaccine studies actually verify that the antibodies produced by the vaccine really have high avidity?
2) Were the low avidity antibodies found in adults with severe 2009 H1N1 disease formed by vaccines or by prior exposure to influenza?
3) Is it really wise to mass vaccinate a whole population making the whole population vulnerable if a similar virus comes along but the antibodies have low avidity?
They sum this up nicely in the Nature news article on the study:
“Nobody really had a good explanation for why middle-aged people seemed to have more severe disease than would have been expected,” says Richard Scheuermann, an immunologist at the University of Texas Southwestern Medical Center in Dallas. “This explanation is the first one that I’ve seen that actually makes sense.”
In light of the findings, Scheuermann cautions against attempts to develop universal vaccines that work against different strains of flu viruses year after year, because they could generate destructive antibodies. Instead, the results may prompt doctors to treat middle-aged flu patients with drugs that inhibit the formation of antibody–pathogen complexes, he says, adding, “Now that we have an understanding of the mechanism of severe disease, we’ll be in a much better position to treat infected people and prevent them from dying.”
What a breath of fresh air. The health authorities should learn a lesson from this and stop their yearly vaccine formulation guessing game and start performing useful scientific research. Finding health solutions that are based on pragmatic and targeted approaches to the actual people at risk is a far more efficient way to save lives and avoid the collateral damage of unnecessary and potentially counter productive mass medication initiatives.
 Monsalvo, A.C., et al, Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nature Medicine (2010)
 Polack, F.P. et al. A Role for immune complexes in enhanced respiratory syncytial virus disease. J. Exp. Med. 196, 859–865 (2002).
 Devey, M.E., and M.W. Steward. 1980. The induction of chronic antigen-antibody complex disease in selectively bred mice producing either high or low affinity antibody to protein antigens. Immunology. 41:303–311.