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Pandemic H5N1 Vaccination With Heterologous Boosters
Recombinomics Commentary 10:06
June 30, 2008
The first two contained a vaccine against the Vietnam strain of bird flu and the most recent was against the Indonesian strain.
The above comments from a reporter in the UK describing his participation pandemic vaccine clinical trials describe approaches being used by a number of companies. The earliest trials, which are now resulting in regulatory approval, started with one of two targets from patients in Vietnam infected in 2004. Both targets were clade 1, which was prevalent in southeast Asia in 2004/2005, when these trials began.
However, virtually all trials produced borderline results, even though the target population was healthy young adults, those most likely to respond positively. Although there was some cross reactivity with clade 2 isolates, which are linked to almost all current reported H5N1 human infections, the cross reactivity was lower than values for the homologous target. Thus, protection against an emerging H5N1 is questionable, since each clade 2 sub-clade has evolved markedly since 2005, and many of these sub-clades have produced fatal infections in humans.
Consequently, several companies are offering boosters to those who participated in the first trial, and the boosters generally are clade 2 isolates, like the clade 2.1 target described above. Recent results presented in Kalua Lumpur indicated that the boosted patients had higher titers against the original clade 1 target, as well as the clade 2 target used in the boost. These boosters were given 1 to 1½ years after the initial set of two immunizations.
The above data raises serious questions about the widespread plans to stockpile vaccines. The first vaccines were approved in the US over a year ago, and these vaccines have a shelf life of 18 months. Thus, in the next several months, these vaccines will expire. Although the vaccines will have offered some insurance for a pandemic that may have happened in the recent past, the discarded vaccines will have no value going forward. Only the small number of patients participating in the trials will have benefits from the formulations using clade 1 targets.
However, the protocol of using the earlier targets as an initial vaccination, followed by boosters using more recent isolates appears to be the most effective method for the generation of more respectable titers, which will have a greater likelihood of providing protection against future H5N1 targets.
Thus, the best use of these expiring vaccines would be to provide initial protection, followed by boosters at future dates. These mismatched vaccines will be best used at the present time. The current plan, which is to stockpile these mismatched vaccines for use after a pandemic begins will likely drive the evolution away from existing or emerging versions of H5N1 and decrease the likelihood of success for vaccines targeting the emerging strain.
Thus, the optimal use of the stockpile vaccines was immunization after earlier regulatory approval, which was done for a small number of patients enrolled in trials. The next best use would be to vaccinate now, before H5N1 is efficiently transmitted in human populations.
Stockpiling mismatched vaccines is likely to produce results which are far from optimal, and will likely produce significant problems related to the efficacy of future vaccines.
Recombinomics Paper at Nature Precedings