Preliminary results from two clinical trials of the 2009 Influenza A(H1N1) vaccine are promising on two counts, vaccine safety and immune responses to the virus, raising hopes of an early breakthrough in finding a vaccine against the infection that has killed close to 3,000 people across the world since April.

The main results from the trials conducted continents apart — Adelaide, Australia, and Leicester, U.K. — are common pointing to the possible global application of the vaccines that are under development.

Despite the different design, dosages, and composition of the vaccine in the two trials, the immune responses produced were good, and the vaccine was found to be safe. While the trial in the U.K used an adjuvant, the Australian one did not.

Tenderness at the injection site was the most common adverse condition observed in both trials. The local adverse reactions seen in volunteers in the U.K. trial were moderately higher than those found on their counterparts Down Under.

An urgent global necessity

Both trials produced good immune responses in volunteers after just one dose of the vaccine. This is very significant as more people can be vaccinated in a mass immunisation programme during a pandemic. There are only a few companies who have reached the clinical trial stage.

The infection has taken healthcare officials around the world by surprise. With no viable preventive measures, the emphasis is on basic hygeine and, in severe cases, isolation of the patient, to prevent the spread of the virus. The commonly prescribed drug, Tamiflu, has only helped in reducing the duration of the infection. The daily death toll of the infection, which continues to rise across countries, underscores the sense of urgency behind the clinical trials. People across the globe will benefit from a successful vaccine as the production capacities of vaccine manufacturers are limited.

“Another advantage of the one-dose schedule is that antibody responses develop sooner,” notes an editorial published in the latest issue of the New England Journal of Medicine. “Achieving protection 3 to 4 weeks earlier with one dose, rather than later on a two-dose schedule, is advantageous. From a logistic standpoint, administering one dose will greatly simplify vaccination programs and should reduce costs.”

The Australian trial using a non-adjuvant vaccine

The trial conducted in Australia by CSL Limited used a vaccine without an adjuvant — a substance added to a vaccine to improve the body’s immune response to vaccine.

A total of 240 volunteers in the 18 to 64 age group were recruited for the trial and were split into two groups of 120 volunteers. Both groups received either 15 micrograms or 30 micrograms of the vaccine.

Preliminary results show that a single dose of the vaccine at both doses “produced a robust immune response in a majority of the subjects,” notes a paper published in the same issue of the journal.

From a public health point of view, using the 15 microgram vaccine will be advisable as more people can be vaccinated.

According to Dr. Michael M. Greenberg, the first author of the study, their results show that a single dose was sufficient to produce good immune response “despite the prevailing assumption that two doses of vaccine would be required.”

The good immune response seen after one dose was “unanticipated” especially since the A(H1N1) is a new influenza strain and people therefore do not have any pre-existing immunity to the novel strain.

The antibody response to the H1N1 virus that was measured prior to the first shot of the vaccination, showed volunteers did not have any antibody response to the virus.

However, the paper notes that exposure to other influenza strains could have provided some pre-existing immunity to the H1N1 strain.

According to the authors, the 2009 influenza A(H1N1) virus shares three gene sequences with the recently circulating seasonal H1N1 virus and with the current seasonal H3N2 virus.

The Leicester trial using an adjuvant vaccine

The U.K. trail, where a Novartis vaccine was used, enrolled 175 adults in the age group 18-50. Volunteers received two doses of an adjuvant vaccine of 7.5 micrograms. The second dose was give either at 7 or 14 days after the first dose.

The two doses were given in different combinations. The interim analysis of the trial deals with the immune responses measured in 100 volunteers after 21 days.

“The vaccine generates antibody response likely to be associated with protection within 14 days after a single dose is administered,” notes the paper published in the latest issue of the New England Journal of Medicine.

Dr. Tristan W. Clark, the first author of the paper, however, cautions that the effect of an adjuvant on the H1N1 strain is still not known.

According the editorial, though two doses combined produced higher antibody level compared with one dose (7.5 micrograms), the immune responses were adequate in at least 80 per cent of the volunteers in every group.

Dr. Clark does not rule out the role of pre-existing immunity against the H1N1 virus. Fifteen per cent of subjects had detectable antibody to the virus prior to vaccination. “Although people with previous respiratory illness were excluded from the trial, asymptomatic infection with influenza A(H1N1) viruses [during the trial] cannot be rule out,” Dr. Clark notes.