August 25, 2006
WHO: Three Clade 2 H5N1 Candidate Pre-Pandemic Vaccines Added to Current Clade 1 Vaccine
Pre-Pandemic H5N1 avian flu vaccine development has become more complex due to the continuing evolution of the H5N1 virus over the past three years. On August 18th the World Health Organization (WHO) posted on their website a detailed update from their May and June 2006 postings on new H5N1 prototype strains for vaccine development. Whereas current clinical trials with the pre-pandemic H5N1 vaccine all use Clade 1 (“genetic group 1”) H5N1 viruses isolated in 2004 from Vietnam, the WHO now recommends use of three (3) more candidate H5N1 vaccines, all of which are Clade 2 H5N1 viruses, specified as “subclades” 1, 2, and 3.
WHO reports that of the six (6) known subclades of Clade 2 H5N1 viruses, three (3) differ in geographical location and have caused most human infections in the latter part of 2005 and in 2006. The 18 August WHO document provides a helpful figure, grouping by name each of these three subclades of Clade 2 H5N1, as well as Clade 1 viruses, termed “Evolution of the H5N1 haemagglutinin gene”.
This document also contains a very useful table that illustrates the very limited cross-reactivity between the antibodies induced in the standard influenza model (the ferret) by the Clade 1 and Clade 2 (subclades 1-3) H5N1 viruses, thus explaining the rationale for developing candidate vaccines against all four of these different H5N1 viruses. This table comparing the antigenic differences in the evolving H5N1 viruses is titled “Haemagglutination Inhibition Reactions of H5N1 viruses”.
Geographically, the WHO notes that human infections with Clade 1 H5N1 viruses (of which there are currently no “subclades”) occurred primarily in 2004-2005 in “Cambodia, Thailand, and Vietnam”.
Although not stated explicitly by WHO, a shorthand nomenclature for these viruses could be: “Clade 1”, “Clade 2.1” (Clade2/subclade 1), “Clade 2.2” (Clade 2/subclade 2.2) and Clade “2.3” (Clade 2/subclade 3).
Geographically, the WHO notes that human infections with H5N1 were caused mainly by clade 1 viruses (of which there are currently no “subclades”) in 2004-12005 in “Cambodia, Thailand and Vietnam”.
In contrast, in later 2005 and 2006 most human infections with H5N1 have been due to Clade 2 viruses, primarily “subclade 1” in Indonesia, “subclade 2 in countries in the Middle East, Europe, and Africa, and “subclade 3” in China. The one exception noted by the WHO is that the H5N1 viruses from the Karo cluster in rural north Sumatra, Indonesia in May 2006 appear “antigencically more closely related to H5N1 viruses in subclade 2” whereas most H5N1 viruses are Clade 2/subclade 1 (“2.1”).
In this 18 August document WHO names for the first time a Clade 2/subclade 3 (“2.3”) candidate vaccine virus, namely A/Anhui/1/2005-like virus.
The impact of this new and evolving WHO information for stockpiling of pre-pandemic H5N1 vaccines appears to be that more than one, and possibly multiple, such vaccines are needed, with all the associated public health, economic, and ethical implications.
Director, Center for Biologic Counterterrorism & Emerging Diseases Washington Hospital Center EROne Institutes
Adjunct Professor of Microbiology and Immunology
Georgetown University Medical Center