Flu pandemics: are we prepared?

The first avian flu controversial paper appeared in Nature last April, and the second one just came out in the last issue of Science. For the occasion, Science also published a series of essays from various experts in the field discussing the issues at stake and what we learned. The most fundamental question is: in case of a flu pandemic, are we prepared?

Rino Rappuoli and Philip Dormitzer discuss what can be done in the event of a flu pandemic, basing their observations on the lessons learned from the 2009 H1N1 (the so called "swine flu") pandemic [1]. In 2009, H1N1 vaccines were successful in reversing the rise of flu cases. However, they became available only after the pandemic had started (8 months after the first case had been reported) and only in wealthy countries.

The authors present four possible preventive approaches.

(1) Pre-pandemic vaccination: in 2009, people exposed by either vaccination or infection to the H1 strain, were able to sustain the H1N1 infection. If a vaccine induces a strong antibody response, those antibodies will work also against distantly related strains, indicating that vaccination against the H5 strain may be able to prevent a possible H5N1 pandemic.

"Because H5N1 infection of humans is so rare, the population has not been primed by previous exposures. This lack of prior exposure makes the population more vulnerable to severe disease caused by highly virulent H5N1 strains and makes immunization more difficult, necessitating the use of adjuvants, higher antigen content, and two doses to elicit sufficient antibody titers."

(2) New cell culture technologies: currently, most vaccines are grown in cell cultures, which is dependable on egg supplies and lengthens the production time. New cell culture technologies would increase the manufacturing capacity of the vaccine, which is needed because mathematical models show that "the proportion of the population that must be immunized for effective immunity is likely to be greater than 80%."

(3) Extended Program on Immunization (EPI): currently only rich countries have broad vaccination policies and not many recommend routine flu immunization. Initiated by the World Health Organization, the EPI program sets goals and a standardized vaccination schedule for all children world-wide. Currently, flu vaccinations are not part of the EPI program, but if they were introduced within the program this would expand the availability of the vaccines beyond the rich countries.

(4) Synthetic seed generation: a viral strain is needed to make a vaccine and cloning these strains takes time. Rappuoli and Dormitzer propose as an alternative synthesizing the genes instead to generate synthetic virus. Novartis, the multinational pharmaceutical both Rappuoli and Dormitzer work for, has an ongoing project to use synthetic genomics that would reduce vaccine production time by up to two months.

"In conclusion, while we wait for the development of a universal influenza vaccine, we have practical options that we could implement today to reduce the risk of mass global mortality from the next influenza pandemic."

[1] Rappuoli1, R, & Dormitzer, P. (2012). Influenza: Options to Improve Pandemic Preparation Science, 336 (6088), 1531-1533 DOI: 10.1126/science.1221466