Findings published online first in The Lancet Infectious Diseases demonstrate that results from two new phase 1 human trials indicate that prime (initial) immunization with a DNA vaccine against H5N1 influenza followed by a booster dose of conventional influenza vaccine has a higher effect than administering two doses of traditional influenza vaccines; a treatment strategy that could be used to fortify against future pandemics.
People with no pre-existing immunity against an emerging virus strain represent the biggest threat for a worldwide outbreak of influenza, making the development and distribution of effective vaccines a vital necessity for the prevention of future pandemics. The H5 antigen is ideal for testing unique approaches to improve the protection of influenza vaccines, as most of the general population is largely naïve to H5N1 influenza.
Julie Ledgerwood and her team from the National Institutes of Health in Bethesda, MD, USA carried out two phase 1 trials, to evaluate safety and immunity responses of a prime-boost influenza vaccination strategy consisting of a vaccine made from DNA encoding the haemagglutinin (HA) from a H5N1 influenza virus before administering a booster dose of the H5N1 monovalent inactivated vaccine (MIV). A monovalent vaccine is designed to immunize against a single antigen or microorganism.
For the trial, researchers randomly administered 81 healthy adults who had no history of influenza vaccination with a dose of the DNA vaccine at day 0 or twice at day 0 and week 4. After this, participants received a MIV booster at 4 or 24 weeks, or a two-dose regimen of MIV with either a 4 or 24-week interval.
Findings revealed that the prime-boost strategy was safe overall with great improvements to the immune response, particularly in those participants where the time between the prime and the boost was extended to 24 weeks.
The researchers discovered that antibodies generated by DNA priming with a 24-week MIV boost interval achieved a protection level of 81% in individuals, whilst the increase in geometric mean antibody titer, a measure of immune response, was over four times higher compared with that of individuals who received only MIV at 4 or 24 weeks.
They noted that the production of neutralizing antibodies that targeted the stem region of the HA protein was stimulated in several individuals administered with the prime-boost regimen; an important discovery because the stem only varies little across different strains of the virus, meaning that antibodies generated against the stem can neutralize multiple influenza virus strains. “A DNA-MIV vaccine regimen could enhance the efficacy of H5 or other influenza vaccines and shows that anti-stem antibodies can be elicited by vaccination in man,” the researchers explain.
Shan Lu from the University of Massachusetts Medical School in Worcester, MA, USA, writes in an accompanying comment:
“These findings are especially important because a major limiting factor in the preparation against pandemic influenza is the restricted manufacturing capacity to produce enough doses of vaccines in a short period of time to cover the population in need. If the vaccination strategy presented in this study was followed, the total amount of traditional vaccines against influenza would be reduced by half, which would allow more individuals to be vaccinated in a timely manner.”
He continues and concludes:
“The report supports the idea of a pre-pandemic vaccination, since various DNA vaccines can easily be mixed together to provide broad coverage against several potential pandemic influenza viruses (even across different subtypes), long before any outbreak. Hosts primed with DNA vaccines are very likely to have reduced morbidity and mortality, even without a boost.”
Written by Petra Rattue