Researchers in Japan have transformed mosquitoes into vaccine-carrying syringes by genetically engineering the insects to express the vaccine for leishmaniasis--a parasitic disease transmitted by the sandfly--in their saliva. According to a study in Insect Molecular Biology, mice bitten by these mosquitoes produced antibodies against the parasite. It's not yet clear whether the immune response was strong enough to protect against infection.

"Following bites, protective immune responses are induced, just like a conventional vaccination but with no pain and no cost," said lead researcher Shigeto Yoshida, from the Jichi Medical University in JapanYoshida, in a press release from the journal. "What's more continuous exposure to bites will maintain high levels of protective immunity, through natural boosting, for a life time. So the insect shifts from being a pest to being beneficial."

Researchers consider the project more of a proof of principle experiment than a viable public health option, at least for now. According to an article on ScienceNow,

There's a huge variation in the number of mosquito bites one person received compared with the next, so people exposed to the transgenic mosquitoes would get vastly different doses of the vaccine; it would be a bit like giving some people one measles jab and others 500 of them. No regulatory agency would sign off on that, says molecular biologist Robert Sinden of Imperial College London. Releasing the mosquitoes would also mean vaccinating people without their informed consent, an ethical no-no. Yoshida concedes that the mosquito would be "unacceptable" as a human vaccine-delivery mechanism.

However, flying vaccinators-or "flying syringes" as some have dubbed them -may have potential in fighting animal disease, says [David O'Brochta, an insect molecular geneticist at the University of Maryland, College Park]. Animals don't need to give their consent, and the variable dosage would be less of a concern.

A number of common supplements and drugs can boost the immune system's ability to ward off the flu and reduce symptoms once you have it, said Jeffrey Gelfand, a physician at Massachusetts General Hospital at the CIMIT (Center for Integration of Medicine and Innovative Technology) Innovation Congress this morning in Boston. Gelfand suggested that in the absence of adequate supplies of vaccine against the H1N1 flu strain, we'll need to turn to less conventional measures. Clinical research shows that L-theanine, which is found in tea, and quercetin, a plant polyphenol, can reduce chances of getting an upper respiratory infection, he said. Both are available at stores that sell vitamin supplements.

Statins, the cholesterol-lowering blockbuster drug, can reduce symptoms of the flu, especially in younger people, the group hardest hit by H1N1. The drugs, many of which are available generically, reduce the "cytokine storm"--part of the immune reaction that occurs during sepsis and influenza infection. "I believe this could significantly reduce mortality," said Gelfand.

Gelfand also said that changing our approach to vaccination could help extend limited vaccine supplies. One method currently under study is delivering vaccines to the skin, rather than to the muscle, as is done with current injections. Directly targeting the skin enhances the response from immune cells in the skin. His team is testing a laser-coupled injection system, in which a precise dose of laser light is used to briefly irritate the skin, attracting the target immune cells even more effectively. Initial studies show that this approach generates the same antibody response with only 20 percent of the amount of vaccine.

An illustration of the hemagglutinin protein (shown in yellow and blue) on the H5 influenza virus H5, bound to a neutralizing antibody (red). Credit: William C. Hwang

Flu shots have to be reformulated every year, thanks to the constantly mutated virus. And the annual vaccine won't protect against more deadly strains, like the H5N1 bird flu. But that may soon change: scientists have now developed antibody proteins that can neutralize different strains of the influenza virus, including the deadly H5N1 bird flu, the virus behind the 1918 epidemic, and common seasonal strains. These new antibodies target part of the virus that is shared between different strains and thus appears to be broadly effective. The research was published on Sunday in the journal Nature Structural & Molecular Biology.

According to an article in Nature,

The antibodies also give researchers clues about how to develop new vaccines. "This opens up the avenue of thinking about universal influenza vaccines, which has not been realistic before", says Peter Palese, an influenza expert at Mount Sinai School of Medicine in New York who was not involved in the work.

A vaccine using this technology could theoretically be used to protect against various types of flu, as well as to treat the virus once a person is infected. Scientists who developed the antibodies say that they hope to have a candidate vaccine to test in humans within the next three years.

But not everyone is as optimistic about the possibilities. According to an article in the New York Times,

Henry L. Niman, a biochemist who tracks flu mutations, was skeptical, arguing that human immune systems would have long ago eliminated flu were the virus as vulnerable in one spot as this discovery suggested. Also, he noted, protecting the mice in the study took huge doses of antibodies, which are expensive and cumbersome to infuse.

[...]

The research began by screening a library of 27 billion antibodies he had created, looking for ones that take aim at the hemagglutinin "spikes" on the shells of flu viruses . . . The flu virus uses the lollipop-shaped hemagglutinin spike to invade nose and lung cells. There are 16 known types of spikes, H1 through H16.

The spike's tip mutates constantly, which is why flu shots have to be reformulated each year. But the team found a way to expose the spike's neck, which apparently does not mutate, and picked antibodies that clamped onto it. Once its neck is clamped, a spike can still penetrate a human cell, but it cannot unfold to inject the genetic instructions that take over the cell's machinery to make more virus. The team then turned the antibodies into full-length immunoglobulins and tested them in mice.