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Weak Immune Response
to Mild Infections Driving Re-Infection?
The above comments from CDC's media update indicate that areas that had high levels of H1N1 in the spring are seeing a resurgence of infections in the fall. One such area is Buffalo, NY which was heavily impacted in the fall, including the deaths of two students who attended schools within a mile of each. H1N1 was confirmed in most zip codes within the city (see map). However, this fall there have been major outbreaks in school districts in or adjacent to Buffalo, raising concerns of re-infections. Such re-infections are supported by anecdotal reports of people infected in the spring and fall, or twice in the fall.
The recently released data on the clinical trial in Australia suggests that such re-infections may be linked to low titers generated during mild infections. Although prior pandemic H1N1 infections were among exclusion criteria, 31% of enrollees had titers of 40 or more at baseline. Since there is little cross reactivity between contemporary seasonal H1N1 and pandemic swine H1N1, the baseline titers are almost certainly due to pandemic H1N1 infections that were not disclosed or not know the enrollee. Since many who are infected experience mild disease, including infections without fever, it is likely that many or most of these enrollees had mild infections.
Figure two suggests that although these enrollees had prior antibodies, the titers were relatively low (the vast majority were between 40 and 160) and most had significant improvements (increases of 4 fold or more) after a single injection, suggesting the weak responses to earlier natural infections would provide limited immunological protection, which would support common re-infections.
These data would also explain the limited level of drift, because naïve hosts as well as those with prior mild infections would be susceptible to re-infections, which would limit the selective pressure offered by genetic drift. Indeed, in recent CDC weekly updates, only one isolate has shown reduced titers to the pandemic vaccine target. However, this recently identified isolate may signal the start or accelerated drift as more of the target population develop higher antibody levels.
Thus, it is likely that H1N1 will continue to expand in areas infected earlier because of a low antibody response in mild cases as well as infection in those who do not develop a robust response to the vaccine.