Whole-Virus H5N1 Vaccine Trial: 69 % safe seroconversion rate
"Whole-Virus H5N1 Vaccine Trial
Larry M. Baddour, MD
Journal Watch Infectious Diseases
June 11, 2008
A phase I and II trial showed that a whole-virus H5N1 vaccine derived from cell culture rather than from embryonated eggs is safe and immunogenic.
The possibility of an H5N1 avian influenza pandemic has been a major global public health concern. --- Potential vaccines to prevent H5N1 infection have shown disadvantages, including poor immunogenicity and long lead times for production. Now, researchers have developed a new strategy for manufacturing an H5N1 vaccine, using tissue culture rather than embryonated chicken eggs.
A manufacturer-designed and -supported clinical trial of the resulting vaccine was conducted in Austria and Singapore. Two hundred seventy-five adult volunteers were enrolled in the randomized, dose-escalation, phase I and II investigation. Two doses of the vaccine were given 21 days apart; each contained 3.75 µg, 7.5 µg, 15 µg, or 30 µg of viral hemagglutinin antigen, with or without adjuvant. Serologic analysis was performed on blood samples collected at baseline, 21 days, and 42 days. For 7 days after each vaccination, participants recorded their daily oral body temperatures, as well as any local reactions or systemic adverse events that occurred.
No serious vaccine-associated adverse events were reported. The most common adverse events included injection-site pain and headache. The best immune response was seen when using the 7.5-µg formulation without adjuvant (, 69%). The vaccine, which was produced with a clade 1 strain (A/Vietnam/1203/2004), also induced neutralizing immune responses against clade 2 and clade 3 strains.
Comment: This study heralds two major accomplishments. One is the potential availability of a safe and immunogenic vaccine against a much-feared pathogen that could produce devastating human losses either through wild-type mutational events or through bioterrorism-related molecular engineering to facilitate human-to-human viral spread. The other is that laboratory advances now allow the use of cell culture, which is preferable to embryonated eggs for virus production in vaccine development.
Citation(s):
* Ehrlich HJ et al. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Engl J Med 2008 Jun 12; 358:2573.
* Wright PF. Vaccine preparedness — Are we ready for the next influenza pandemic? N Engl J Med 2008 Jun 12; 358:2540."
Larry M. Baddour, MD
Journal Watch Infectious Diseases
June 11, 2008
A phase I and II trial showed that a whole-virus H5N1 vaccine derived from cell culture rather than from embryonated eggs is safe and immunogenic.
The possibility of an H5N1 avian influenza pandemic has been a major global public health concern. --- Potential vaccines to prevent H5N1 infection have shown disadvantages, including poor immunogenicity and long lead times for production. Now, researchers have developed a new strategy for manufacturing an H5N1 vaccine, using tissue culture rather than embryonated chicken eggs.
A manufacturer-designed and -supported clinical trial of the resulting vaccine was conducted in Austria and Singapore. Two hundred seventy-five adult volunteers were enrolled in the randomized, dose-escalation, phase I and II investigation. Two doses of the vaccine were given 21 days apart; each contained 3.75 µg, 7.5 µg, 15 µg, or 30 µg of viral hemagglutinin antigen, with or without adjuvant. Serologic analysis was performed on blood samples collected at baseline, 21 days, and 42 days. For 7 days after each vaccination, participants recorded their daily oral body temperatures, as well as any local reactions or systemic adverse events that occurred.
No serious vaccine-associated adverse events were reported. The most common adverse events included injection-site pain and headache. The best immune response was seen when using the 7.5-µg formulation without adjuvant (, 69%). The vaccine, which was produced with a clade 1 strain (A/Vietnam/1203/2004), also induced neutralizing immune responses against clade 2 and clade 3 strains.
Comment: This study heralds two major accomplishments. One is the potential availability of a safe and immunogenic vaccine against a much-feared pathogen that could produce devastating human losses either through wild-type mutational events or through bioterrorism-related molecular engineering to facilitate human-to-human viral spread. The other is that laboratory advances now allow the use of cell culture, which is preferable to embryonated eggs for virus production in vaccine development.
Citation(s):
* Ehrlich HJ et al. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Engl J Med 2008 Jun 12; 358:2573.
* Wright PF. Vaccine preparedness — Are we ready for the next influenza pandemic? N Engl J Med 2008 Jun 12; 358:2540."
