While the Covid-19 pandemic is ongoing, another public health threat, antibiotic resistance, continues unabated. Microbiologists and chemists from two universities in Hong Kong recently made a breakthrough in synthesizing the first vaccine against one of the most deadly antimicrobial resistant pathogens, Acinetobacter baumannii (A. baumannii). The vaccine shows good protection against the superbug in mice, indicating great potential as a vaccine for humans.

 

A. baumannii is a Gram-negative bacterium that can cause a range of infections in both hospitals and the community and has a high mortality rate. It is particularly hazardous to immunocompromised patients. It is multi-drug resistant and exhibits extensive resistance to most first-line antibiotics. Thus, the development of new antibacterial agents is urgently required. In 2017, the World Health Organization (WHO) published its first-ever list of antibiotic-resistant “priority pathogens”, which was a catalogue of 12 families of bacteria that pose the greatest threat to human health. A. baumannii was listed as a top priority for promoting the research and development of new antibiotics to save lives.

Top-listed Superbug

But as the proverb says, prevention is better than cure. A lot of scientists have tried to make vaccines against A. baumanii, and pseudaminic acid (Pse) has long been a research focus. Pse is the surface glycan of A. Baumannii, helping the bacteria to evade the body’s immune system. So the capsular polysaccharide from A. baumannii containing Pse has been regarded as a potential target for vaccine development.

However, vaccine development progress was hampered by many obstacles, such as the structural variety and complexity of bacteria surface glycan and the difficulty in extracting enough Pse-containing polysaccharide samples in high purity from cultured bacteria.

Co-led by Professor Chen Sheng, Associate Dean (Research) of the Jockey Club College of Veterinary Medicine and Life Sciences (JCC) and Professor of Veterinary Bacteriology at CityU, and Professor Li Xuechen from the Department of Chemistry at The University of Hong Kong (HKU), the research team recently overcame the barriers by chemically synthesizing Pse conjugates in high purity (with little contamination from other chemicals) for the first time with advanced techniques.

Chemical synthesis to overcome barriers

The team chemically combined the synthesized Pse with a carrier protein to enhance the immunogenicity of a small antigen to make Pse conjugates a vaccine, and then tested it in mice. Their experiments demonstrated the critical role of Pse as an effective antigen to elicit a high immune response and create antibodies. Their analysis showed that there was a high level of anti-Pse antibodies in the mice sera after the mice received the vaccine. The immunized mice were completely protected from infections caused by A. baumannii, while all the mice in the control group died within 36 hours.

“The data indicated the high potential for the application of chemically synthesized Pse conjugates as a vaccine against Pse-bearing pathogens, and a great alternative for the control of clinical infections caused by the superbug A. baumannii, for which current treatment options are still extremely limited at the moment,” said Professor Chen.

Promising alternative to fight superbugs

The team has applied for a patent for the invention and will further evaluate its potential in preclinical studies.

“The ongoing Covid-19 pandemic can create a perfect storm for antibiotic infections in healthcare settings, with more patients staying in hospital for a longer time and more resources being diverted to respond to the pandemic,” said Professor Chen. “So we need to find ways to continue the fight against multi-drug resistance issues. With ready access to the synthetic Pse now, the development and mass production of a Pse-based vaccine against A. baumannii infection is becoming more feasible. This study showed that a vaccine is a great alternative for the control of clinical infections caused by multi-drug resistant pathogens like A. baumannii.”

The study was published in ACS Central Science, titled “Synthetic pseudaminic acid-based antibacterial vaccines exhibit effective protection against Acinetobacter baumannii”.

The first authors are Dr Wei Ruohan and Miss Yang Xuemei. The corresponding authors are Professor Chen and Professor Li. The study was funded by the Research Grants Council of Hong Kong and the Health and Medical Research Fund.

DOI number: 10.1021/acscentsci.1c00656