Trial sheds light on lower VSV-EBOV doses

A trial to see if a lower dose of one of the leading Ebola vaccine candidates can reduce reactions such as arthritis and skin rashes found that the effects persisted and that decreasing the dose had a negative impact on immune response. An international research team based in Switzerland published their findings on the lower VSV-EBOV dose yesterday in an early online edition of Lancet Infectious Diseases.

VSV-EBOV uses a vesicular stomatitis virus (VSV) to deliver the Ebola virus glycoprotein. The vaccine was developed by Canadian researchers and is licensed by NewLink Genetics and Merck. The findings on problems with the lower dose come just days after a ring vaccination trial of the vaccine in Guinea found that it was highly effective against Ebola, putting the wheels in motion for it to be used as a response tool in the outbreak region. The vaccine reactions came to light last December during earlier phase 1 studies, which led to a temporary pause.

The team looked at the safety profile of a reduced dose of 3×105 plaque-forming units (PFU), compared to 1×107 PFU or 5×107 PFU. The lower dose prompted significantly lower antibody levels against Ebola glycoprotein compared to the higher dose. Researchers also found that at the lower dose, the VSV vector was still seemingly able to seed peripheral tissues, which could explain arthritis, dermatitis, and vasculitis. About 25% (13 of 51) of study subjects had arthritis about 10 days after vaccination, but some didn't have measurable VSV viremia, hinting that the vector might target synovial tissue. Some of the low-dose participants with arthritis also had a rash or dermatitis.

Given the results, the team concluded that lowering the VSV-EBOV dose isn't a strategy for preventing the vaccine-induced reactions.

In an editorial in the same issue, Julie Ledgerwood, DO, chief of the clinical trials program at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center, wrote that the researchers have produced revealing data from a meticulous investigation that also included joint aspiration and skin biopsies to probe the cause of the adverse events. She is also the primary investigator for trials of ChAD3, the other Ebola vaccine in phase 3 trials. It uses a chimpanzee adenovirus vector and was developed by NIAID and GlaxoSmithKline (GSK).

She said the study and its findings show how complex the design and implementation of an early phase clinical trial can be and how important it is to collect solicited adverse events. The bulk of Ebola vaccine studies have shown that the Ebola antigen is safe and not linked to adverse events, and further vector attenuation could improve the side effect profile, Ledgerwood wrote. However, she noted that the approach raises more questions on how such steps would affect immunogenicity.
Aug 3 Lancet Infect Dis abstract
Aug 3 Lancet Infect Dis editorial extract


81 ill, 7 dead from legionellosis in New York borough

An ongoing outbreak of Legionnaires' disease in the South Bronx that began in mid-July has sickened 81 people and killed 7, according to an ABC News story today. An overflow crowd attended a town hall meeting last night in the area to gain answers about the.

The New York City Department of Health and Mental Hygiene (DHMH) announced the launch of an investigation into the outbreak in a Jul 29 press release. At that time, there were 31 known cases and 2 fatalities.

All of the fatal cases have occurred in older adults with underlying medical conditions, according to a CNN story yesterday. Sixty-four people have been hospitalized.

Water from cooling towers and other possible sources of Legionella are being tested, said DHMH, and five buildings, including a hospital and a hotel have tested positive so far, said CNN. The buildings have been cleaned, and the sites are submitting long-term plans for prevention of future growth of the bacteria.

Legionellosis, which is not transmitted person to person, causes flu-like symptoms, including fever, chills and cough. Health Commissioner Dr. Mary Bassett has urged anyone with respiratory symptoms to seek medical help, CNN said.

New York City's water supply is reportedly safe and residents are not at risk, according to Bassett.
Aug 4 ABC News story
Aug 3 CNN story
Jul 29 DHMH press release

Input sought from FDA on raw milk cheese practices

In an effort to identify and evaluate measures that could minimize the impact of harmful bacteria in cheese made from unpasteurized milk, the Food and Drug Administration (FDA) on Jul 31 issued a 90-day request for comments from the public that began yesterday.

Comments can include scientific data and information and are expected to aid the FDA in learning about the many and diverse standards and practices of the broad range of cheese producers, including those making artisanal cheeses.

The risks accompanying consumption of cheese made from unpasteurized milk are greatest for immunocompromised persons, the elderly, pregnant women, and children, says the FDA's Jul 31 announcement of the comment period.

The FDA's action is based in part on findings of a joint FDA/Health Canada study released Jul 31 "that included estimates for both countries of the number of servings resulting in one case of invasive listeriosis, prevalence of contaminated servings, and level of increased risk of invasive listeriosis per serving of raw milk cheese," explained a story today in Food Safety News (FSN).
Jul 31 FDA constituent update
Aug 4 FSN story
Jul 31 FDA/Health Canada risk assessment


Study finds benefits to coadministering HPV, Tdap, and meningitis vaccines

Administration of three childhood vaccines—9-valent human papillomavirus (9vHPV), tetanus/diphtheria/acellular pertussis (Tdap), and meningitis—in a single visit is effective and safe and may facilitate uptake, according to a report yesterday in Pediatrics.

Researchers at 41 sites administered the vaccines to children ages 11 to 15 in a randomized, open-label study.

A group of 621 children received the first 9vHPV dose and the Tdap and meningitis vaccines on the first day of the study, while a group of 620 received 9vHPV on the first day and returned a month later for the Tdap and meningitis vaccines. The ratio of boys and girls in each group was nearly equal.

Both groups experienced similar results, with more than 75% showing a fourfold rise in titers to all four meningitis serogroups, 99.8% having acceptable diphtheria and tetanus titers 4 weeks after vaccination, and 100% demonstrating HPV seroconversion.

A significantly higher proportion of children who received all three vaccines on the first day reported swelling at the HPV vaccine injection site (14.4%, compared with 9.4% in the control group).

On the basis of these results, researchers determined that coadministration of all three childhood vaccines was noninferior to administering them separately. Because children and teens make infrequent healthcare visits, administration of the vaccines in one visit may increase uptake and adherence.
Aug 3 Pediatrics study


Positive vaccination messages effective in changing skeptical attitudes

Messages that promote the positive effects of measles vaccination are more effective at changing negative attitudes toward childhood vaccines when compared with messages that refute the opinions of vaccine skeptics, according to a study published yesterday in the Proceedings of the National Academy of Sciences (PNAS).

In response to the threefold increase in 2014 US measles cases (644 cases in 2014), psychologists from the University of Illinois at Urbana-Champaign and the University of California, Los Angeles, tested the effects of different vaccine messages on a sample of 315 people.

Researchers assigned study participants to one of three groups. The first group was given a mother's story about her child contracting measles; photos of children and infants with measles, mumps, and rubella; and fact sheets about the importance of vaccination in preventing illness. The second group received facts about recent research refuting links between vaccination and autism, and the third group received scientific information unrelated to vaccination.

Participants exposed to stories, photos, and illness prevention information in the first group experienced a significant increase in their support for measles vaccination. Attitudes in the groups exposed to autism risk or unrelated information did not change.

Researchers said that results support the use of vaccine messages that are nonconfrontational and remind people of vaccination's role in preventing serious illness.
Aug 3 PNAS study

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