Unveiling the unexpected role of nonprotective antibodies in vaccine efficacy challenges traditional perspectives and offers a potential game-changing insight for future vaccine research.

Humans are typically exposed to Staphylococcus aureus (SA) bacteria within the first few weeks of their life.

It’s estimated that around 30% of people carry this very common bacteria, and most infections are harmless. However, SA infections are also a serious public health concern.

Finding a vaccine for SA has been a priority for decades. Over the years, numerous vaccines have failed during clinical trials. Although multiple studies have found success during preclinical phases with experimental models, no vaccine has been successful in human clinical trials. In a study published on January 16, 2024, in Cell Reports Medicine, researchers at the University of California, San Diego, School of Medicine, offered an explanation for this continued vaccine failure.[3]

Researchers from the University of California, San Diego, hypothesised that one such adaptation might be that SA bacteria are able to trick the body into releasing nonprotective antibodies when they first infect or colonise humans. As a result, these antibodies would be recalled when someone is vaccinated, causing the vaccine to be ineffective—and potentially explaining why vaccines that work in experimental models don’t work in humans.

The laboratory experimental model used in trials is bred to be free of specific pathogens and typically has little to no exposure to SA before trials, a stark contrast to humans who frequently coexist with SA.[3][4]  

To test this theory, researchers collected blood samples from healthy volunteers and then quantified, and purified the anti-SA antibodies in the samples. The extracted SA antibodies were then transferred to the experimental model.

The researchers found that vaccines were ineffective in the experimental model that received anti-SA antibodies as well as the experimental model that had previously been exposed to SA.

However, vaccines were effective for experimental models that were not exposed to either SA or human antibodies. The researchers’ results matched those of failed clinical trials.[3]

Vaccine advancements

Vaccines have been in the spotlight over the past few years. Vaccine development was a crucial element of response during the height of the COVID-19 pandemic, with the first vaccines being approved by the United States Food and Drug Administration (FDA) on December 11, 2020. The COVID-19 vaccine’s rapid development and implementation wasn’t only noteworthy for its effect on the pandemic.

The vaccines approved for COVID-19 were the first mRNA vaccines, and their success could open the door to vaccines for a range of other infections. The theory behind mRNA vaccines has been in development for decades, and virologists have now seen it in action.[5] 

“Scientists had been working on the idea of this since about the 1980s. This was decades ago that people came up with the idea of using RNA as a potential vaccine,” says Ivan Martinez, MD, who specialises in virology at the West Virginia School of Medicine.

“Scientists were already investing effort and companies were already investing money to develop these vaccines against SARS, the flu, infection bacteria, and other infections. So for people in the virology field, this isn’t new at all; it’s been in development, but now it’s fully here. Now the potential is being seen.” 

Researchers have already begun investigating how the technology behind COVID-19 vaccines could be applied to HIV, hepatitis, Zika, Epstein-Barr, and more. 

Two additional vaccine approvals in recent years further demonstrate significant research advancements. On May 3, 2023, the FDA approved Arexvy, the first respiratory syncytial virus (RSV) vaccine approved for use in the United States. Arexvy was approved for adults 60 years of age and older.

Vaccinations are now also available for children aged 24 months and younger with certain conditions that place them at high risk for severe RSV disease and for pregnant people. In October 2021, the World Health Organisation (WHO) recommended a malaria vaccination, RTS,S, for children under 2 living in malaria endemic areas. The WHO, which expanded its recommendations in 2023, estimates that nearly 2 million children in Ghana, Kenya, and Malawi have received the RTS,S vaccination.[6][7][8] 

Disclaimer: This story is contributed by Stephanie Srakocic and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.