Although the 2009 H1N1 influenza A viral pandemic spread rapidly due to the lack of pre-existing immunity in much of the human population, older adults appeared to be relatively protected due to pre-existing cross-protective antibodies that were most likely generated in response to natural infection with 1918 H1N1 and its early derivatives.5
Here, we show that commercial preparations of IVIG, produced prior to the 2009 H1N1 pandemic, contain cross-reactive antibodies against 2009 H1N1 as assessed by both HI and MN assays. In addition, we found that administration of high-dose IVIG significantly increased the levels of cross-reactive HI and MN antibodies against 2009 H1N1. Thus, commercially available IVIG produced prior to the pandemic could potentially be used as an adjunctive treatment for 2009 H1N1 infection in severe cases or in patients with limitations in adaptive immunity. Since newer IVIG preparations will likely include plasma from donors who have been vaccinated for 2009 H1N1 or who were infected with 2009 H1N1, the HI and MN antibody titers will likely increase. However, our results indicate that such inclusion is not necessary for IVIG to provide substantial passive immunity to 2009 H1N1, and suggest that the approach of using existing IVIG preparations might also be considered in future influenza pandemics or if highly drifted strains circulate.
Although there has been no reported clinical experience with the use of passive antibodies in treating 2009 H1N1, there were many attempts to use convalescent blood products in treating acute influenza during the influenza pandemic in 1918. The therapeutic administration of blood products enriched in anti-influenza antibodies appeared to confer a survival advantage particularly if the treatment was given within the first four days of illness.11
In addition, convalescent plasma has been used anecdotally for severe H5N1 infection.12
Furthermore in animal models, therapeutic monoclonal anti-influenza IgG antibodies have been shown to clear influenza virus after infection in SCID mice, which lack B cells and T cells.13
Thus, it is plausible that the therapeutic administration of immunoglobulin containing neutralizing antibody against 2009 H1N1 could aid in halting the progression of infection as well as in viral clearance.
Passive immunotherapy for 2009 H1N1 influenza and other pandemic influenza A strains may be of particular importance in cases of anti-viral resistance. While the 2009 H1N1 virus has remained largely susceptible to the neuraminidase inhibitors, oseltamivir and zanamivir, there have been sporadic reports of oseltamivir-resistant strains. Resistance has been particularly frequent in hosts with impaired adaptive immunity who shed virus for prolonged periods,14
and for whom adjunctive therapy with IVIG could be particularly useful.
In summary, we have identified significant titers of cross-reactive antibody against 2009 H1N1 in commercial preparations of IVIG despite the low prevalence of pre-existing cross-reactive immunity in the general population. Administration of high-dose IVIG increased the serum titer of these antibodies, and this may be a useful adjunctive therapy in severe infections with 2009 H1N1 influenza, particularly in the immunocompromised, those who are refractory to neuraminidase inhibitor therapy, and immunologically naïve children.