Tuesday, May 26, 2009

A Boost for Avian Flu Vaccination

A Boost for Avian Flu Vaccination

Priming population increased response by 25%

FOR YEARS NOW, SCIENTISTS, POLITICAL LEADERS, and the global community have dreaded and planned for a potential outbreak of H5N1 avian influenza. Their fears are justified: The highly infectious disease rapidly mutates from one generation to the next, each generation composing its genetic structure to defend itself against the vaccinations that challenged its predecessors. H5N1 is particularly deadly, having killed 60% of its human victims.

As soon as scientists pinpoint how to kill off the form (or "clade") of the disease on which they based their formulas, a new clade evolves that resists the vaccination. Although a global pandemic could erupt if the disease were to mutate into a form that is communicable among humans, a new approach may help prevent such a frightening possibility. Priming populations before the spread of the disease could help their rate of response to a one-dose vaccination in the event of a pandemic.

The response rate to one dose was very low, but when you have a primer and then have a single dose the result is usually positive. It'S that comparison that says priming helps.

-John J. Treanor, MD, University of Rochester Medical Center

New research reveals that administering booster vaccines against new strains of H5N1 to subjects who were primed with a prior vaccination is more likely to result in a positive response to a single-dose treatment than administering a two-dose course of treatment without priming.

"The study looked at whether a previous vaccine influences how you respond to a single dose," John J. Treanor, MD, a professor of medicine, microbiology, and immunology at the University of Rochester Medical Center, tells Pharmaceutical Formulation and Quality. Dr. Treanor worked on the study with colleagues from his institution, from The EMMES Corp. (Rockville, Md.), and from the Southern Research Institute (Birmingham, Ala.).

The H5N1 virus.

"The response rate to one dose was very low, but when you have a primer and then have a single dose the result is usually positive. It'S that comparison that says priming helps," says Dr. Treanor. Subjects who had a booster fared even better than those primer-na�ve subjects given the full course of treatment, though Dr. Treanor and his colleagues are unsure why. "The fact that they responded so well was a bit of a surprise."

Both the booster and the initial vaccine were developed based on the genetic properties of two distinct clades of H5N1-A/Hong Kong/1997 (H5N1, clade 0) and A/Vietnam/1203 /2004 (H5N1, clade 1). The disease'S inherent defense mechanism could now be overcome if priming and vaccination continue to prove effective regardless of the variance of clades between the two stages of treatment.

As they reported in the September 1 issue of the Journal of Infectious Diseases, Dr. Treanor and colleagues administered a single dose of clade 1 of H5N1 to patients who had been injected with two doses of the vaccine for clade 0 of H5N1 in 1998. Researchers measuring serum antibodies prior to vaccination as well as 28 and 56 days afterwards detected a 68% positive response to the booster in the geometric mean titer (GMT) of those who had been primed with the clade 0 vaccination, compared to a 43% positive response among those not primed.

Some of the results are likely what Treanor calls artifacts of the small number of subjects in the study; these could be elucidated by future studies that include larger groups of subjects.

Dr. Treanor stressed that the present study includes no assessment of the pros and cons of implementing a pre-vaccination or vaccination program against avian influenza. Rather, he says, the information is useful because it demonstrates the potential impact of issuing primer vaccines before a single dose.

"It doesn't say that you should do it. That'S a policy decision.... What it boils down to is whether we're likely to see a pandemic, and is that risk at such a level that we should pre-vaccinate people."

The researchers are now investigating the immunological reason for the subjects' response to the primer. According to Treanor, the research may very well result in the development of new tools for seasonal influenza, because the technology, time, and effort put into studying bird flu may be useful in developing new vaccination methods to treat this ailment as well.

-Lucy Randall

Drug Delivery Solution From the Sea

A sponge could help battle cancer

AN INTERNATIONAL TEAM of marine biology researchers has found that a species of Fijian sponges has significant drug delivery applications, specifically for the treatment of cancer. When the sponge Reneira sarai competes for space on the crowded ocean floor, it uses rare natural polymers to ensure that no invaders grow on its surface. By making the pores of its cell membranes temporarily permeable, the species is able to sense invaders and shut them out, thereby preventing their growth. A biologic drug based on material taken from Reneira sarai will most benefit solid, localized tumors, which lack the vasculature needed for other types of drugs.

"In the future, we hope to use this to deliver drugs directly into tumors by permeabilizing the cells to accept anti-cancer drugs," says Marcel Jaspars, PhD, of the Marine Biodiscovery Centre at the University of Aberdeen in Scotland.

Dr. Jaspars and his international team hope to help drug manufacturers understand and implement their findings so that cancer therapies can open and close targeted tumor cells during treatment. Dr. Jaspars presented the team'S findings in July at the Society of Experimental Biology'S Annual Main Meeting in Marseille, France.

"We found a compound from a Mediterranean sponge called Reneira sarai that has nothing growing on it-the compound it uses to keep itself from being fouled or infected turns out to be an unusual natural polymer," he says. "We have shown this makes polymers in cell membranes that can be used to pass pharmaceuticals, DNA, and proteins into cells."

In his presentation in Marseille, Dr. Jaspars called attention to the pressing need for effective drug delivery methods in the biologics market. "A major factor limiting the development of some new drugs, such as membrane-imper-meant small molecules, is intracellular delivery to their sites of action," he says.

The sponge Reneira sarai.


The product the researchers envision would deliver a wider variety of distinct macromolecules and drug-like small molecules into the intracellular compartment than any existing product allows. The highly stable, water-soluble material the researchers have developed has special potential because it exists in synthetic variants, allowing pharmaceutical developers to customize their products for a variety of drug delivery and cancer treatment applications.

While seeking cures for a specific illness helps in targeting the most pressing medical needs in order of priority, the team decided to work backwards from their observations, following whatever leads proved most promising and adapting to their results. This admittedly "hap-hazard" and "uninformed" biodiscovery method yielded the crucial discovery.

The researchers must now confront the challenge of obtaining sufficient sample material for the required follow-up studies. Possible solutions include synthesis, semi-synthesis, and culture of the symbiont. So far they have achieved the most success by looking at the expression of the biosynthetic pathway in a bacterium.

Although the stages between discovery and release to market are often slow and complicated when dealing with nature-based drug treatments, the researchers can manufacture the materials in the lab and issue them to interested companies. Dr. Jaspars estimates that these findings will be influencing drug delivery for tumor treatment in five to 10 years

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