Birdflu Mailing List: Maybe a vaccine will provide some protection though not perfectly matched !!!

[William Weir (weirwilliam]

Forwarded from:  Richard N. Danila,  Deputy State Epidemiologist, and Section 
Chief 
Acute Disease Investigation and Control, Minnesota Department of Health
625 Robert St., P.O. Box 64975, St. Paul, MN  55164-0975
Phone: (651) 201-5414 - Fax: (651) 201-5743 - Pager: 1-888-487-7097

Forwarded from CBN Editor <cbn_editor [at] 
upmc-biosecurity.org<mailto:cbn_editor [at] upmc-biosecurity.org>>
Clinicians' Biosecurity Network Report, October 4, 2006. 

Published by the Center for Biosecurity of UPMC to present analysis of 

recent events in biosecurity for healthcare providers
CBN Report:  Might H5N1 Vaccine Cross Protection Allow for Pre -Pandemic 
Vaccine Stockpiling?
by Eric Toner, M.D. and Luciana Borio, M.D, October 4, 2006 

There have been doubts as to whether our government's strategy to stockpile 
vaccine in bulk in advance of a pandemic will be beneficial. This is because 
influenza A viruses are constantly mutating and drifting antigenically; 
therefore, any vaccine stockpiled in advance would not be well matched to the 
eventual pandemic strain.

For example, the first major H5N1 vaccine trial conducted in the U.S. used a 
vaccine derived from a clade 1 H5N1 virus (the strain found in Vietnam, 
Thailand, Cambodia and Laos); however, in vitro testing indicates that this 
vaccine does not appear to induce protective antibodies against clade 2 H5N1 
viruses (the strain found everywhere else) [1]. Because it takes approximately 
6 months or more from the isolation of a new pandemic influenza virus until 
vaccine specific to that strain becomes available using current egg based 
technology, it is now widely assumed that an effective pandemic vaccine will 
not be available for many months after a pandemic begins. As a consequence, 
pandemic planning has mostly focused on public health measures for disease 
containment and medical care for the ill.
However, recent experiments in ferrets conducted by Dr. Robert Webster's group 
at St. Jude Children's Research Hospital have yielded promising results that 
suggest that even a vaccine that is not perfectly matched to a circulating 
strain may still provide some degree of cross protection. If there is 
significant cross protection among H5 strains in humans, then it is sensible to 
stockpile a generic H5 vaccine before the onset of a pandemic.
Evidence of cross protection in the ferret model
In the July 15 issue of the Journal of Infectious Disease [3], Govorkova and 
colleagues report on experiments conducted on ferrets which demonstrated two 
important findings, (1) vaccination against one H5N1 strain resulted in 
significant cross protection against antigenically distinct H5N1 strains and 
(2) this cross protection was not always detectable by the usual in vitro 
testing for the presence of antibodies. Ferrets were immunized with one or two 
doses of inactivated whole-virus vaccine produced by reverse genetics with the 
hemagglutinin and neuraminidase genes of an H5N1 virus isolated in Hong Kong in 
2003 (A/HK/213/03 virus). The ferrets were subsequently challenged with lethal 
doses of a virus isolated in Vietnam in 2004. All the vaccinated animals 
lived*even those who had received only one dose of vaccine. The ferrets that 
received only one dose of vaccine had no detectable HI or neutralizing 
antibodies against the Vietnam virus, but were nevertheless protected from 
death. As the authors point out, the primary purpose of a pandemic vaccine is 
to reduce deaths, not necessarily to prevent infections.
Possible benefits of stockpiling
Even a vaccine that is only partially protective could have significant impact 
on the consequences of a pandemic. In a mathematical model by Longini and 
colleagues, early use of a poorly matched vaccine that still partially reduces 
transmission resulted in significant mitigation of the outbreak [2]. In 
addition, a reduction in the severity of disease, even without an accompanying 
reduction in the actual number of people infected, would have a significant 
impact on the consequences of a pandemic by reducing the burden on the 
healthcare system.
Priming with H5 antigen
A related strategy to stockpiling a "generic" H5N1 to be used at the start of a 
pandemic is that of "H5 priming" vaccination. In this strategy, a generic H5 
antigen is included in the annual flu shots before the actual pandemic in the 
hope that recipients would either (1) develop some partial cross-immunity to an 
eventual H5 pandemic strain or (2) require only one dose of a pandemic vaccine 
rather than the two-dose course shown by clinical trials to be necessary now. 
This strategy could offer significant logistical advantages, but uncertainties 
remain, including whether the next pandemic will be caused by an H5 strain.  
Conclusion
Clearly, much more research is needed before this preliminary animal study can 
be used to guide policy.  For example, it is not known whether these results 
from ferrets can be extrapolated to humans and whether the benefit shown with 
whole-virus vaccine would extend to split-virus vaccines. Nonetheless, the work 
reported by the St. Jude group is encouraging and offers some hope that H5N1 
vaccines currently in development could significantly mitigate the potentially 
catastrophic consequences of a severe H5N1 pandemic.
References
[1] Poland GA. Vaccines against Avian Influenza * A Race against Time. N Engl J 
Med. 2006;354:1411-3. Available at 
http://content.nejm.org/cgi/content/full/354/13/1411<http://content.nejm.org/cgi/content/full/354/13/1411>.
 

[2] Germann TC, Kadau K, Longini IM, Macken,CA. Mitigation strategies for 
pandemic influenza in the United States. PNAS 2006;103: 5935-5940. Available at 
http://www.pnas.org/cgi/content/full/103/15/5935<http://www.pnas.org/cgi/content/full/103/15/5935>.

[3] Govorkova EA, Webby RJ, Humberd J, Seiler JP, Webster RG. Immunization with 
reverse-genetics*produced H5N1 influenza vaccine protects ferrets against 
homologous and heterologous challenge. J Infect Dis 2006;194:159-67. Available 
at 
http://www.journals.uchicago.edu/JID/journal/issues/v194n2/35777/35777.html<http://www.journals.uchicago.edu/JID/journal/issues/v194n2/35777/35777html>.