9 June 2005

H5N1 Vaccines:=20 Update

= =20 In April the first human H5N1 vaccine trials began at three study = sites=20 in the USA: UCLA, University of Rochester, New York and the University = of=20 Maryland. This study is supported by the US National Institutes of = Health. A=20 total of 450 vaccinees, assigned to study arms using different doses of = H5N1=20 antigen, without any vaccine adjuvant, are being enrolled. This study = represents=20 a critical first step on the road to producing a large stockpile of a = safe and=20 effective human vaccine against the H5N1 influenza virus that is now=20 increasingly cited as the possible precursor of the next=20 pandemic.

=20 Dr. Klaus Stohr provided an update May 18, 2005 for the WHO on=20 anticipated additional H5N1 vaccine studies by the end of December = 2005. In addition to the one ongoing = study in=20 the USA he cited other nations planned H5N1 vaccine = studies:

Japan: 4 companies are planning to initiate = coordinated=20 studies using vaccines that are =93antigen sparing=94 (i.e., attempt to = use the=20 least amount of H5N1 antigen in the vaccine that produces an effective = immune=20 response and is clinically safe. = Each of the studies cited by Stohr may include use of adjuvants = e.g.,=20 substances such as =93alum=94, (the only FDA-licensed vaccine adjuvant) = to boost the=20 immune response to a vaccine antigen, or experimental, non-FDA-licensed=20 adjuvants.

Australia: one = company,=20 antigen-sparing (H5N1) vaccine, with adjuvant(s).

France: one company,=20 antigen-sparing (H5N1) vaccine, with adjuvant(s)

Canada: one company,=20 antigen-sparing (H5N1) vaccine, with adjuvant(s)

=20 In an April 7, 2005 report by the Secretariat of the WHO to the=20 58^th World Health Assembly on =93Strengthening pandemic = influenza=20 preparedness and response=94 it was noted in item 24 (page 5 of 7) two major potential ways of = H5N1 vaccine=20 =93antigen-sparing=94:(1): Intradermal vaccination, and (2): Use of a = vaccine=20 adjuvant. In addition, testing different doses of H5N1 antigen in the = prototype=20 studies, such as the one begun in the USA in April 2005 in different age = groups=20 and possibly in immunocompromised as well as immunocompetent patient = populations=20 will be critical to maximize the protective immune response using the = minimum=20 necessary amount of H5N1 vaccine.

=20 One a pandemic begins the April 7, 2005 WHO report noted that = production=20 of the usual yearly trivalent influenza vaccine (e.g., H3N2, H1N1, and = an=20 influenza B strain) will stop and production, if possible, of a = monovalent=20 (e.g., H5N1) pandemic influenza vaccine will start. Unlike yearly flu = shots,=20 however, two doses of the pandemic influenza vaccine (e.g., H5N1) may be = needed=20 to stimulate a protective immune response in many people. Logistically, = such a=20 two-immunization requirement would be very difficult to achieve in any = given=20 nation, let alone globally.

Daniel R. Lucey, MD,MPH

Director, Center for Biologic Counterterrorism and = Emerging=20 Diseases

Washington Hospital Center

Adjunct Professor of Microbiology and=20 Immunology

Georgetown University school of = Medicine

Washington, DC