A phase 1 clinical trial of Valneva's VLA15 Lyme disease vaccine candidate shows that it is safe and produces a strong but waning immune response against the six most common strains of the Borrelia burgdorferi bacterium in Europe and the United States.

Valneva researchers led the trial, which was published yesterday in The Lancet Infectious Diseases. The team studied adverse effects and antibody responses among 179 healthy adults aged 18 to 40 years in Belgium and the United States after receipt of three doses of VLA15 from January 2017 to January 2019.

Participants received either a version adjuvanted with alum to improve the antibody response or a non-adjuvanted version in doses of 12-, 48-, or 90-micrograms (μg).

Immune response up to 1 year

VLA15 was safe and well tolerated up to 1 month after the third dose, with mostly mild or moderate adverse events. These events were more common in the 48- and 90-μg groups (range, 28 to 30 participants [94% to 97%]) than in the 12-μg group (25 participants [86%]) in both the adjuvanted and non-adjuvanted groups.

Common local reactions included injection-site tenderness (151 [84%] participants; 356 events) and pain (120 [67%]; 224), and the most common systemic reactions were headache (80 [45%]; 112), fatigue (45 [25%]; 56), and muscle pain (45 [25%]; 57).

The vaccine marshaled immune responses for all strains, but responses were greater in the higher-dose adjuvanted groups (geometric mean titer [GMT] at 90 μg with alum, 61.3 to 321.7 units per milliliter [U/mL] vs 23.8 to 111.5 U/mL at 90 μg without alum). One month after the third dose, GMTs declined, reaching baseline by 1 year. A booster dose given 13 months after the first dose triggered a strong immune response for about 6 months.

We eagerly await the results of the next clinical trials.

In a commentary in the same journal, Ondrej Hajdusek, PhD, and Jan Perner, PhD, of the Czech Academy of Sciences, said that although annual VLA15 boosters would be required to maintain protection against Lyme disease, the vaccine "represents a milestone in our fight against Lyme disease, and we eagerly await the results of the next clinical trials."

In an ongoing investigations into the source of H5N1 avian flu in a rash of cat deaths in Poland, scientists found the virus in one of five submitted chicken meat samples that the cats ate. Polish media reports about the findings prompted pushback from the country's agriculture officials and the poultry industry, according to official statements translated and posted by Avian Flu Diary, an infectious disease news blog.

Some of the sickened cats were kept indoors, leading to questions about how they contracted the virus. Ahead of a media report, Polish virologists in a July 3 Twitter post explained that they tested five submitted chicken samples from cat owners, one of which yielded the virus. They said they couldn't determine if the meat was contaminated before or after the customers opened the product.

Today, Poland's agriculture ministry posted a statement that said the media report overinterpreted the virologist's findings and also emphasized the safety of Polish poultry products and that the food-chain link to the cat illnesses isn't proven.

Poultry outbreaks in Togo and Poland

In other H5N1 developments, Togo reported an outbreak at a poultry farm in Golfe prefecture, which is near the country's capital city of Lome, according to a notification yesterday from the World Organization for Animal Health (WOAH). The virus killed nearly all of the 1,500 birds at the farm, and the remaining ones were culled.

Elsewhere, Poland reported an H5N1 outbreak that began on June 29 at a poultry farm in Matopolskie province, which killed 14 of 127 susceptible birds, according to notification today from WOAH.

Infectious disease consultation (IDC) was associated with a 40% reduced risk of death in gram-negative bacteremia patients, according to a multicenter study published yesterday in Clinical Infectious Diseases.

To evaluate the impact of IDC on outcomes in patients with gram-negative bloodstream infections (GN-BSI), a team of US researchers conducted a retrospective observational study on GN-BSI patients admitted to 24 US hospitals from January to December 2019. All sites had an active antimicrobial stewardship program with physician and pharmacy leadership, but none had mandatory IDC for GN-BSI, and stewardship interventions and guidelines for GN-BSI varied. The primary exposure was IDC versus no IDC, and the primary outcome was 30-day mortality.

Overall, there were 4,861 GN-BSI episodes, of which 2,814 (54%) had IDC; 681 (14%) resulted in 30-day mortality (12% vs 17% in IDC and no IDC, respectively).

Expanding infectious disease knowledge and training is essential.

After propensity score weighting to account for unmeasured confounders, patients who had an IDC had significantly reduced risk of 30-day mortality (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.47 to 0.77), and the reduced risk persisted at 90 days (HR, 0.70; 95% CI, 0.57 to 0.86). There was no difference in risk of 30-day readmission for patients with or without an IDC (HR, 1.09; 95% CI, 0.77 to 1.54) or risk of 30-day recurrent bacteremia (HR, 1.33; 95% CI, 0.70 to 2.52)

"IDC plays an important role in the management of GN-BSI, and expanding infectious disease knowledge and training is essential," the study authors wrote. "Until then, understanding where and when this limited resource is most beneficial is needed."

The National Institutes of Health (NIH) said today that the first clinical trial of a 3-month treatment regimen for tuberculosis (TB) is closing enrollment because of a high rate of unfavorable outcomes.

The randomized controlled CLO-FAST trial sought to evaluate the safety and efficacy of a 3-month regimen containing clofazimine and high-dose rifapentine compared with the standard 6-month regimen. The trial began in November 2021 and had enrolled 104 of 185 planned participants in Haiti, India, Malawi, South Africa, and Zimbabwe.

While the study's independent Data Safety and Monitoring Board (DSMB) determined there were no safety concerns with the investigational regimen, an interim analysis found participants taking the 3-month regimen experienced ongoing or recurring TB rates above thresholds set in the study protocols, which led DSMB to recommend closing enrollment. The National Institute of Allergy and Infectious Diseases, part of the NIH accepted the recommendation.

"Identifying shorter TB treatment regimens is crucial for limiting the spread of infection, reducing drug resistance, improving quality of life for people with TB disease, and reducing demands on health systems worldwide," the NIH said in a news release. "The interim results of the CLO-FAST trial do not support advancing this specific regimen for further evaluation, but the study data will provide essential evidence to inform TB science."

Identifying shorter TB treatment regimens is crucial for limiting the spread of infection, reducing drug resistance, improving quality of life.

NIH noted that participants who were randomized to receive the investigational regiment will complete the treatment as planned, then take an additional 3 months of rifampin and isoniazid. Participants who already successfully completed the regimen will be monitored closely to ensure they remain TB-free.