Protection against H1N1 and H5N1 in mice and ferrets is expected to last for three to six months

Precious time lost in developing an effective vaccine against influenza A viruses that jump from animals to humans and spread across the world causing a pandemic is quite close to becoming history.

According to a study published today (May 30) in the Science Translational Medicine journal, an effective vaccine would be available for use against influenza virus in a matter of weeks.

This is a far cry from the current situation where scientists are ill-equipped to immediately develop an effective vaccine when an influenza virus strikes. This was in full display when the H1N1 pandemic struck in 2009.

Researchers from the University of Pennsylvania, U.S. who completed trials on animals — mice, ferrets and monkeys — have got promising results. Phase I trials on humans to study the safety of the vaccine could well begin any time.

Unlike the current strategy of developing a vaccine from scratch based on the strain causing the epidemic or pandemic, researchers from the University of Pennsylvania, U.S. have developed a vector-based vaccine that produces broadly neutralizing antibodies that will be equally effective against influenza strains — H5N1 and H1N1 — that have jumped from animals.

The researchers applied the same principle used in many HIV vaccine trials across the world, India included. They selected F16, a previously isolated broadly neutralizing antibody to influenza A, and introduced it into an adeno-associated virus (AAV) vector to deliver the antibody into the body.

An earlier study had shown that F16 introduced into mice provided protection against H1, H3 and H5 viruses.

But can F16 antibody remain effective despite the many reassortments and mutations that occur in the viruses? “We do not propose using exclusively the FI6 antibody but rather emphasize the uniqueness of our approach for rapidly constructing and producing AAV vectors that can express a neutralizing anti-influenza antibody soon after its isolation, which is especially important in the case of a pandemic,” clarified Dr. Maria P. Limberis in an email to this correspondent. Dr. Limberis is from the University of Pennsylvania, and is the first author of the paper.

To achieve the best results, the researchers introduced the antibody at the site of infection, in this case, the nasal route. “For mice and ferrets expression [of the broadly neutralizing antibody] in the nasopharynx was sufficient for protection,” noted Dr. Limberis.

In trials on mice, the controls that did not get the vaccine lost weight “rapidly” and had to be killed; those that got the vaccine showed no weight loss and none died.

But the best part was that the protection against influenza A virus was achieved in a short span of three, four or seven days after being vaccinated. Though the animals lost some weight, they recovered.

The ability of the animals (mice) to survive the onslaught of three different H5N1 pandemic strains were tested. The AAV vector containing F16 antibody was able to protect the mice against all three strains; there was no trace of the virus in the body at the end of the 28 days.

Similar results were achieved in the case of two H1N1 strains. “What we observed in mice was either complete absence of the virus or a 1,000 to 1,00,000-fold reduction in viral load [in the case 2005 Indonesian H5N1 and 2009 Mexico H1N1 viruses],” Dr. Limberis noted.

In the case of ferrets, similar results were obtained in the case of both H5N1 and H1N1. “For ferrets, protection against influenza was achieved within seven days of nasal delivery of the AAV9 vector,” she said. “The level of protection was similar for both [mice and ferrets] animal models.”

Aside from the effectiveness and the almost immediate protection, the duration of protection is also equally important. “[In the case of mice and ferrets] based on similarly designed studies using surrogate reporter genes we expect the duration of protection against H1N1 and H5N1 to be in the order of 3-6 months,” noted Dr. Limberis.

But will the F16 antibody be effective against H7N9 as well? “I expect FI6 antibody expressed via AAV9 vector and delivered intranasally to be effective against H7N9. These studies are in progress,” Dr. Limberis explained.

In the case of humans, she expects the AAV vector with neutralising antibody to be present throughout the nasopharynx to confer the same level and duration of protection. “This needs to be carefully evaluated,” she noted.

This article has been corrected for an editing error.