Scientists discover why staph vaccines don’t work in humans

Scientists discover why staph vaccines don’t work in humans The sometimes pathogenic bacterium Staphylococcus aureus has a long and intimate relationship with humans, a relationship that helps it stave off our immune response.

Staphylococcus aureus is a common bacterium that is harmless, for the most part, posing no threat to humans they coexist with. However, on occasion, it can turn into an opportunistic pathogen, causing food poisoning or skin and blood infections. Scientists have searched for an effective staph vaccine for more than a century, including at least 15 successful preclinical studies using animal models over the past 30 years. However, these Staph Vaccine candidates all failed in subsequent human trials. “It’s a long-standing problem and one of the most puzzling problems in the staph field,” said George Liu, MD, PhD, professor of pediatrics at the University of California San Diego School of Medicine. (UCSD) and Chief of the Division of Infectious Diseases at Rady Children’s Hospital-San Diego. “None of these human trials worked, and scientists have struggled to find a reason.”

The problem has become increasingly urgent with the emergence of methicillin-resistant S. aureus (MRSA), a type of staph bacteria that has become increasingly resistant to antibiotics typically used to treat common staph infections. MRSA has spread to become the main source of acquired infections in hospitals and other health care facilities, such as nursing homes. In fact, a study published in 2022 estimated that bacterial resistance to antimicrobials led to tens of millions of infections and 1.2 million deaths worldwide in 2019, with MRSA being the main driver.

Vaccines are the most effective way to reduce this health burden and reduce antibiotic resistance,” Liu said, highlighting the successes of infant inoculations and more recent COVID-19 vaccines. In a new paper, published July 7, 2022 in the journal Cell Host & Microbe, lead author Liu and colleagues say they may have found the answer to the S. aureus riddle, including the mechanism which explains why vaccine trials have failed so far and ways to overcome this. Fundamentally, the difference lies in prior exposure to the pathogen, the authors write. Laboratory mice used in research are engineered (bred/bred/maintained) to be free of the specific target pathogen; they had little or no exposure to S. aureus before vaccination. In contrast, humans are very quickly exposed to S. aureus after birth. Within two months of birth, half of babies harbor active colonies and abundant antibodies to fend off most infections.

Along with first author Chih-Ming Tsai, PhD, a project scientist in his lab, and others, Liu hypothesized that if lab mice without previous exposure to S. aureus respond well to potential vaccines because they are completely new, human versions do not work. because S. aureus has developed defenses to repel a therapeutic attack. “Vaccines against staph seem so easy to make in lab mice because they rarely see S. aureus, but humans are exposed to staph within the first few weeks of life, and in order to coexist, staph seems to have evolved many strategies to render our immune response against them ineffective,” Tsai said. “If the mice had staph infections before vaccination, we think the candidate vaccines might not work.” To test their hypothesis, Liu, Tsai and their co-authors conducted a series of experiments simulating one of the largest failed staph vaccine trials in humans, which targeted the IsdB protein used by S. aureus to acquire the iron necessary for functioning.

Source: This news was originally published by scitechdaily

Comments are closed.