Inactivated yellow fever vaccine potentially safe alternative to live-attenuated vaccine

Monath TP. N Engl J Med. 2011;364:1326-1333.

An inactivated, non-replicating, yellow fever vaccine was effective and did not cause major adverse events associated with the live-attenuated vaccine, according to Thomas P. Monath, MD.

“This could be a major step forward in providing travelers with a safer alternative to the live-attenuated vaccine,” study researcher Monath, of Kleiner, Perkins, Caufield & Byers in California, told Infectious Disease News.

In the randomized, double blind, placebo-controlled, dose-escalation phase 1 study, Monath and colleagues assessed the safety, tolerability and immunogenicity of the inactivated yellow fever vaccine in 60 otherwise healthy adults aged 18 to 49 years (58% were men; 68% were white) who were not previously vaccinated against yellow fever.

Participants were assigned two injections of either a 4.8 mcg high-dose or 0.48 mcg low-dose version of the new vaccine, 21 days apart, compared with placebo. Levels of neutralizing antibodies were measured at baseline and again on days 21, 31 and 42.

The development of neutralizing antibodies was induced in 88% of participants assigned to the low-dose group vs. 100% of those assigned to the high-dose group. Moreover, on day 10 after the second injection of the vaccine, antibody levels were increased in the high-dose group compared with the low-dose group (146 vs. 39; P<.001).

Adverse events were more common in both vaccine groups vs. placebo and included mild pain, tenderness and itching at the injection site and one case of urticaria on day 3 after the second injection of the high-dose version.

“Data show that the new, non-replicating vaccine can elicit protective immunity; however, it takes two doses to accomplish this, whereas the current vaccine elicits immunity in one dose,” Monath said. “Yellow fever vaccine is administered in travel clinics, and these clinics need to inform patients of the risks and benefits of vaccine alternatives. The current vaccine is associated with rare, but fatal vaccine accidents, and the new vaccine is unlikely to cause such events. The travel medicine physician should advise patients accordingly.”

The researchers said the next steps in the development of the vaccine include assessment of the durability of antibody response indicated in the current study and initiation of a phase 2 study.

Disclosure: Dr. Monath is the director of Xcellerex and own shares in the company.

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