Sanofi, Janssen to partner on extraintestinal pathogenic E coli vaccine

News brief

French drug maker Sanofi announced today that it has entered an agreement with Janssen Pharmaceuticals to develop and commercialize a vaccine for extraintestinal pathogenic Escherichia coli (ExPEC).

Under the agreement, Sanofi will pay Janssen $175 million upfront, and the two companies will co-fund future research and development costs for ExPEC9V, a 9-valent ExPEC vaccine developed by Janssen. The experimental vaccine is currently being tested against placebo in a phase 3 trial to evaluate its efficacy in preventing invasive E coli disease (IED) caused by ExPEC9v O-serotypes in patients over 60 years of age.  

E coli is the most common gram-negative bacterial pathogen in humans and is commonly found in the gastrointestinal (GI) tract. But it can move outside the GI tract and enter normally sterile parts of the body, like the urinary tract and the bloodstream, and cause IED. ExPEC strains cause an estimated 10 million cases of IED annually and are also a leading cause of sepsis, particularly in older adults with chronic illnesses. 

In addition, a rise in multidrug-resistant ExPEC strains in recent years has contributed to increased treatment failure and mortality.

E. coli is a significant cause of sepsis, mortality, and antimicrobial resistance in older adults, and the number of cases is rising as the population ages," Thomas Triomphe, Sanofi's executive vice president for vaccines, said in a company press release. "In line with our commitment to design and deliver first- or best-in-class medicines and vaccines, this agreement with Janssen aims to positively impact public health by reducing hospitalization costs and the burden on health systems associated with ExPEC and help older adults around the world to live longer, healthier lives."

CARB-X to fund development of new treatment for antibiotic-resistant pneumonia

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Doctor looking at chest x-ray
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CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) announced today that it is awarding researchers at the University of Melbourne $1.75 million to develop an oral therapeutic that could restore the activity of antibiotics used to treat pneumonia.

The award will support development of PBT2, an ionophore therapeutic that was originally developed as a treatment for neurodegenerative disorders but has since been found to disarm bacterial mechanisms of resistance to first-line antibiotics for community-acquired bacterial pneumonia (CABP), like doxycycline and amoxicillin. Rising resistance has rendered these antibiotics increasingly ineffective.

"We’re grateful for CARB-X's support, providing an accelerated pathway for the development of this new therapeutic to render these drug-resistant bacteria susceptible to existing antibiotics again," Sharon Lewin, MD, PhD, director of the University of Melbourne's Peter Doherty Institute for Infection and Immunity, said in a CARB-X press release

Impact of drug-resistant pneumonia

A global analysis of deaths that were caused by and associated with antimicrobial resistance (AMR) found that more than 400,000 people died in 2019 from antibiotic-resistant lower respiratory infections, including CABP.

"Bacteria that cause community-acquired pneumonia are becoming increasingly resistant to antibiotics on the WHO [World Health Organization] model list of essential medicines, and so we've taken a strategy that embraces both the development of new antibiotics and the pursuit of other products that aim to restore the utility of the ones we already have," said CARB-X Research and Development Chief Erin Duffy, PhD.

The PBT2 project is the first project to receive a grant from CARB-X's 2022-2023 funding call. Since its founding in 2016, CARB-X has funded 92 early-stage antibacterial and diagnostic development projects in 12 countries.

We’re grateful for CARB-X's support, providing an accelerated pathway for the development of this new therapeutic to render these drug-resistant bacteria susceptible to existing antibiotics again.

Record dengue deaths in Bangladesh include more than 100 children

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Save the Children, an international health organization, today said children have been hit hard in Bangladesh's ongoing dengue outbreak, with at least 113 pediatric deaths reported so far.

About 225,000 cases have been reported in the current outbreak, more than 38,000 of them children, and people younger than 20 make up 30% of all dengue cases. So far, more than 1,000 deaths have been reported.

Bangladesh child
Rama George-Alleyne/World Bank/Flickr cc

Save the Children, which is working in six urban areas in Bangladesh, said younger children are more vulnerable to the virus because their immune systems aren't fully developed, and they have more exposure when they play outside and don't sleep under mosquito nets. The group added that kids younger than 5 are especially at risk of severe symptoms, including dehydration and shock.

Lima Rahman, MBBS, Save the Children's health director, said, "Dengue is a relentless enemy, particularly when it comes to our children and their families. Its impact reaches far beyond the physical suffering of the infected child. It disrupts their education, puts immense economic and emotional pressure on families, and strains our healthcare systems."

The group said the surge in dengue cases in Asia is linked to the climate crisis. Dhaka, the country's capital, has experienced its highest temperatures in six decades, followed by monsoon rains. The El Nino weather pattern is expected to exacerbate rising temperatures in Asia, which increases the risk of mosquito-borne diseases such as dengue. They called on high-income countries to increase their support for lower-income countries that are struggling with the burden of dengue disease.

Florida reports more local dengue cases

In its latest weekly surveillance update, the Florida Department of Health reported 7 more locally acquired dengue cases, raising the year's total to 38. The state typically reports sporadic local cases each year.

Of the 38 cases so far, 33 are from Miami-Dade County. The other cases were from Broward, Hardee, and Polk counties.

California law limiting medical exemptions from kindergarten vaccines offset by COVID, alternative schooling

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Young boy after vaccination
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From 2019 to 2021 in California, the proportion of kindergarteners with medical exemptions from school vaccination mandates fell, but the percentage not current with vaccinations rose, probably due to COVID-19–related disruptions and parents opting for homeschooling or other modalities not subject to the requirements, University of North Carolina researchers report in JAMA.

The team analyzed data from the California Department of Public Health's Kindergarten Immunization Assessment reports for the 2019-2020, 2020-2021, and 2022-2022 school years.

The researchers noted that after California eliminated nonmedical exemptions from school-entry vaccination requirements in 2016, medical exemptions rose rapidly, raising questions about inappropriate use. California Senate Bills 276 and 714 (collectively, SB276) became law in January 2021, increasing the state's oversight of medical exemptions.

Enhanced monitoring, assessment needed

The proportion of California kindergarteners not up to date with required vaccinations increased from 5.71% (31,669 children) in 2019 to 7.15% (34,723) in 2020, then decreased to 6.01% (30,290) in 2021. The percentage of medically exempted kindergarteners fell from 0.95% in 2019 to 0.27% in 2021.

Enhanced monitoring and assessment may be necessary to ensure children who fell behind on vaccinations during the pandemic receive them before school entry.

The proportion of kindergarteners overdue for vaccination climbed from 1.48% in 2019 to 2.27% in 2021, as did that of children not subject to vaccine requirements (1.62% to 2.13%). Increases in kindergarteners not up to date rose over 0.5% in 26 of 58 counties, and 8 counties saw an increase of over 2%, namely in Northern California. But the percentage of those not up to date decreased by over 0.5% in 13 counties.

Medical exemptions to vaccination declined at least 0.5% in 19 counties and climbed at least 0.5% in 4, while 13 counties experienced an increase of 0.5% or greater in children not subject to vaccination requirements, and 2 saw a decline of 0.5% or greater.

"The increase in kindergarteners not subject to vaccination requirements after SB276 nearly offset the decrease in medical exemptions," the authors wrote. "Enhanced monitoring and assessment may be necessary to ensure children who fell behind on vaccinations during the pandemic receive them before school entry," they added.

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