A new paper focusing on the long-standing World Health Organization (WHO)-recommended test for the potency of rabies vaccine indicates that it may not be the best method for testing the vaccine, and that another method would be more effective and use fewer animals.

Rabies has been eradicated in many European countries, and even in those developed countries like the United States where the disease still exists, vigorous immunization campaigns, especially in dogs, have brought the number of rabies-related human deaths down to only a handful each year. Still, the estimated human morbidity in developing countries remains high, killing roughly 50,000 or more annually.

One reason for successful rabies treatment in developed countries is that the vaccine can be effectively administered after exposure to the virus. The WHO recommends that newly manufactured lots of human and veterinary rabies vaccine be tested by an in vivo mouse test called the 'National Institutes of Health rabies vaccine potency test' or 'NIH test.'

Although this test is widely regarded as 'adequate,' it is not ideal. There has been concerted effort, for instance, to develop a replacement test that uses fewer or no animals at all. Beyond this, the NIH test has been criticized for its potential to produce inaccurate vaccine potency ratings because its method of vaccine administration and challenge do not adequately mimic actual immunization practice or natural infection routes.

Now, a study published in the 30 November 2006 issue of Vaccine lends credence to the idea that the NIH test should be re-evaluated and possibly replaced. The study, led by Peter Wunderli at ImmunoGen (Cambridge, MA), evaluated experiments performed in the 1990s comparing the accuracy of the NIH test to that of another measure of vaccine potency, the rabies peripheral challenge (RPC) test. Although the RPC test is also an in vivo test, it has the advantage of more closely mimicking routine immunization and natural infection, and uses fewer mice.

The study found that the RPC test picked up significant differences in potency between sequential lots of manufactured vaccine that were missed by the NIH test. Moreover, the RPC test was able to evaluate the protection offered by recombinant-based subunit vaccines, something the NIH test cannot do. As Wunderli tells Lab Animal, adopting the RPC test would mean “fewer mice, more sensitivity, a simpler testing and approval process for current vaccines, and more cost effective recombinant-based subunit vaccines.” To win widespread approval for the RPC test, however, a larger collaborative international study still must be conducted to compare the RPC test to other in vivo testing methods.