Flu Scan for Oct 03, 2013

News brief

Study: H3N2 infection, but not vaccine, disrupts H3N2v spread

Neither the seasonal trivalent (three-strain) influenza vaccine (TIV) nor a monovalent H3N2 vaccine substantially reduced shedding of variant H3N2 (H3N2v) virus in ferrets, but previous infection with a seasonal H3N2 virus did, according to a study yesterday in the Journal of Virology.

Researchers from the US Centers for Disease Control and Prevention (CDC) vaccinated 18 ferrets, which are considered good models for flu in humans, with TIV. They also immunized 6 ferrets with one of two monovalent H3N2 vaccines and 3 with an H3N2v monovalent vaccine.

All of the monovalent-vaccinated ferrets and half of the TIV ferrets were then challenged with an H3N2v virus, while the other half of the TIV group was challenged with a seasonal H3N2 strain.

After challenge, the authors checked the seroconversion status of contact ferrets to assess virus shedding. In the TIV group, 6 of 9 contact ferrets converted when exposed to the H3N2v-challenged animals, compared with 4 of 9 in the H3N2-challenged ferrets.

In the monovalent groups, 5 of 6 ferrets that had contact with the H3N2-vaccinated animals seroconverted, compared with none of the 3 ferrets that had contact with the H3N2v-vaccinated animals. Also, all 6 ferrets that had close contact with 6 unvaccinated ferrets that were then either challenged with H3N2 or H3N2v seroconverted.

In the non-vaccine arm of the study, the investigators infected 12 ferrets with a seasonal H3N2 virus. Six weeks later they challenged 6 ferrets with the same seasonal H3N2 strain and 6 with H3N2v.

As expected, 0 of 6 ferrets that had contact with the H3N2-infected animals seroconverted, but similarly only 1 of 6 ferrets that had contact with the H3N2v-infected animals seroconverted, indicating low H3N2v shedding in those ferrets.

The authors conclude, "The data demonstrate in ferrets that the efficiency of A(H3N2)v transmission is disrupted by pre-existing immunity induced by seasonal H3N2 virus infection."
Oct 2 J Virol abstract

DARPA pursuing RNA-based drugs to fight emerging diseases

The US Defense Advanced Research Projects Agency (DARPA) has awarded Moderna Therapeutics of Cambridge, Mass., up to $24.6 million to develop its RNA therapy platform to make antibody-producing drugs that would combat emerging infectious diseases and biological threats, according to a Fierce Biotech story yesterday.

This grant will support research for up to 5 years to advance Moderna's antibody-producing drug candidates into preclinical testing and human clinical trials. In March, DARPA awarded Moderna $700,000 in "seed" funds to begin work on the project.

Moderna's novel platform works by tapping into the body's cells and turning them into antibody producers, a response that could be used to combat a wide range of diseases, the story said.

The grant is part of a DARPA program aimed at developing new platform technologies that could be safely and rapidly deployed to the US population in the event of an infectious disease outbreak like pandemic flu or a biological weapons attack, even if the pathogen or infectious agent were not known.
Oct 2 Fierce Biotech story

In related news, CureVac, of Frankfurt, Germany, which has developed a new class of therapies and vaccines based on messenger RNA, announced today that it will be collaborating with Janssen Pharmaceutical Companies to develop an influenza vaccine based on CureVac's RNActive technology.

RNActive vaccines, based on CureVac's technology platform, have demonstrated safety and effectiveness in several clinical trials, according to a company press release. Preclinical studies were published in Nature Biotechnology in December 2012, CureVac said.

Under the terms of the collaboration, CureVac will develop optimized RNActive vaccines based on proprietary antigen sequences from Crucell Holland B.V. (a Janssen subsidiary) and test them in various models.
Oct 3 CureVac press release

News Scan for Oct 03, 2013

News brief

Cell study shows potential for broad-spectrum antibiotics for MERS

A two-drug combination may be effective against Middle East respiratory syndrome coronavirus (MERS-CoV), according to the results of a cell-culture study published today in the Journal of Infection.

Chinese and US researchers used small compound-based forward chemical genetics to screen known drugs against flu as well interferons, nelfinavir, lopinavir, and nitazoxanide because of their reported anti-coronavirus effects. They identified 10 as good possibilities against MERS-CoV on the basis of high-throughput screening.

Of those, only mycophenolic acid exhibited high selectivity and low EC₅₀, a common measure of a drug's efficacy that means low doses may be effective. Ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity, but the antiviral effect of interferon-beta-1b was stronger than that of ribavirin.

The authors conclude, "Interferon-beta-1b with mycophenolic acid should be considered in treatment trials of MERS."

In April a US and Canadian team using cell-culture techniques determined that ribavirin combined with interferon-alpha-2b might constitute a good MERS treatment approach.
Oct 3 J Infect abstract
Apr 18 Scientific Reports abstract

Pills containing fecal bacteria may stop recurrent C diff bouts

A small trial showed that taking pills containing fecal bacteria cured patients who had recurrent Clostridium difficile (C diff) infection by balancing intestinal bacteria, according to findings presented at the IDWeek 2013 infectious diseases meeting in San Francisco today.

University of Calgary researchers reported that all 27 patients who took the pills had no recurrence of C diff, even though all of them had had at least four bouts of the infection before treatment, according to an IDWeek press release.

The patients ingested from 24 to 34 capsules containing fecal bacteria, often donated by family members. To make the pills, the researchers processed the feces until they contained only bacteria, and then encapsulated the material in a three-layer gelatin capsule so that it would dissolve in the small intestine rather than the stomach.

This process offers a potential advantage over current methods like fecal transplantation via enema or colonoscope, because it covers more of the intestinal tract, does not involve invasive and more costly procedures, and is more comfortable for patients, according to lead author Thomas Louie, MD, professor of medicine at the University of Calgary, Alberta.

"The pills are a one-shot deal and seem to work. They are easier for patients and are well-tolerated," Louie said in the press release. "It's an exciting development in the field and could possibly even be used to maintain the balance of bacteria in the [gastrointestinal] system in patients at risk for C diff."

The Centers for Disease Control and Prevention, in a recent groundbreaking report on antibiotic resistance, named C diff one of the three most urgent US infectious disease threats.

Lobby pushes for more reworking of FSMA rules

The United Fresh Produce Association (UFPA) has joined an effort of the National Association of State Departments of Agriculture (NASDA) calling for the Food and Drug Administration (FDA) to issue revised proposals surrounding the Food Safety Modernization Act (FSMA) before the final rules are issued, says a story in today's Food Safety News. The story is based on information in yesterday's Hagstrom Report, a subscription-based agricultural news service.

The president of UFPA, Tom Stenzel, was to present the plan to the FDA yesterday but was unable to because of the government shutdown, according to the story.

The effort is aimed at the Produce Safety and Preventive Control rules now in draft form and open to public comment through Nov 15. The main concern is that domestic food producers not be jeopardized by the new rules in relation to importers.

Stenzel claims that the new plan from NASDA and UFPA, rather than being a delaying tactic, is a way of addressing the extensive comments and complexity of the act and making sure it is effective, the story says.

The FSMA, the first large-scale overhaul of food safety laws in more than 70 years, was signed into law in January 2011, and the FDA has been working through the rules for implementation ever since, with controversy over delay of the final rules.
Oct 3 Food Safety News story
Aug 15 CIDRAP News scan item on FSMA rules postponement
Jul 26 CIDRAP News story on FSMA import rules

Imported malaria among London residents declines but remains high

Half the 1,378 imported malaria cases reported in the United Kingdom in 2012 occurred among London residents, with the large majority acquired during travel to Africa to visit family in their country of origin, says a report from Public Health England (PHE).

A common belief among people born in malaria-endemic countries, says a PHE press release, may be that they assume they have natural immunity to the disease and so do not need prophylaxis when traveling there. In reality, immunity wears off quickly once a person leaves an endemic area, the release says.

Estimates of the London population born abroad were nearly 37% for 2011, according to the PHE report. Imported malaria cases in the city numbered 676 in 2012, a rate of 8 per 100,000 residents. This represents a decline in incidence compared with 2011, which was reflected across the United Kingdom, but is still of concern since the disease is highly preventable, the PHE said.

From 2000 to 2012, 88% of imported cases in London were acquired in sub-Saharan Africa, says the report. Nigeria was the most common destination, accounting for 45% of the imported London cases over that period. Fully 80% of infected persons for whom information was available had not taken any prophylaxis before travel. Summer travel was common, which is the high-transmission rainy season in West Africa.

The largest portion of the 2012 London cases were in residents of southeast London, particularly Southward and Greenwich. It is likely, according to the release, that a large number of persons in those areas are of black African ethnicity so may be more likely to travel to Africa.

Interventions, including pretravel education and chemoprophylaxis, can prevent the disease and should be encouraged among those traveling to malaria-endemic areas, particularly Nigeria, advises the report.
Oct 2 PHE press release
Oct 2 PHE full report