Bernard Moss
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
The potential use of smallpox
as a biological weapon has led to the production and stockpiling of a tissue
culture produced smallpox vaccine. Another public health goal is the licensure
of a safer vaccine that could benefit the millions of people advised not to
take the current one because they or contacts have increased susceptibility
to severe vaccine side effects. As smallpox has been eradicated, new vaccines
cannot be tested for efficacy and licensure will necessarily include comparative
immunogenicity and protection studies in animal models. Here we compare the highly
attenuated modified vaccinia virus Ankara (MVA), originally derived by Anton
Mayr, with the licensed live Dryvax (Wyeth) vaccine in mouse and monkey models.
In both models, two doses of MVA induced antibody binding and neutralizing
titers and T-cell responses that were equivalent or higher than induced by
Dryvax. Mice were completely protected against a lethal intranasal administration
of a pathogenic strain of vaccinia virus. Studies with knockout mice indicated
that either antibodies or T cells were sufficient for protection. After challenge of monkeys with monkeypox virus, unimmunized
animals developed greater than 500 pustular skin lesions and became gravely
ill or died, whereas vaccinated animals were healthy and asymptomatic, except
for a small number of transient skin lesions in animals immunized only with
MVA. Because the correlates of smallpox protection are unknown, our findings
of similar humoral and cellular immune responses to MVA and Dryvax in non-human
primates and substantial protection against a severe monkeypox virus challenge
are important steps in the evaluation of MVA as a replacement vaccine for
those with increased risk of severe side effects from the standard live vaccine
or as a pre-vaccine.