The Fight Against Pneumonia and Antibiotic Resistance: Vaxdyn and the K-Vax Vaccine Candidate Against ‘Klebsiella pneumoniae’

Pneumonia is a form of acute respiratory infection typically caused by viruses or bacteria. It can result in mild to life-threatening illness in people of all ages, but it remains the leading infectious cause of death among children globally, according to the World Health Organization (WHO). Antibiotic resistance is a critical issue in treating pneumonia and other infections, making treatment significantly more challenging and less effective, thereby increasing the risk of complications and mortality.

Currently, six bacterial pathogens are responsible for 73% of global bacterial infection-related deaths (over five million in 2019). All of these pathogens share high levels of antibiotic resistance and pathogenicity. Of these, a vaccine exists only for pneumococcus. Vaxdyn has successfully developed vaccine candidates targeting four of the five remaining bacteria, with K-Vax, the most advanced candidate, aimed at disease caused by Klebsiella pneumoniae. This bacterium can cause pneumonia, particularly in hospitalized patients and those with compromised immune systems. Pneumonia caused by Klebsiella pneumoniae is associated with increased severity and risk of complications compared to other types of pneumonia.

“Klebsiella pneumoniae causes severe infections in hospitals due to its strong ability to develop antibiotic resistance mechanisms. It’s a unique bacterium that has acquired a potent mix of genes: virulence genes that enable it to evade the immune system and antibiotic resistance genes that prevent us from halting the infection,” explains Juanjo Infante, CEO of Vaxdyn. “It predominantly affects people with chronic conditions, such as kidney disease requiring catheter use, those undergoing major surgeries, cancer treatments, or chronic lung disease requiring ventilation, focusing on pneumonia. For other bacterial pneumonia, more treatment options and time for trial and error are usually available.”

Klebsiella pneumoniae’s high capacity to acquire antibiotic resistance genes “quickly leaves us without treatment options,” Infante notes, adding, “There is a type of Klebsiella known as hypervirulent, capable of killing young, immunocompetent individuals outside hospital environments.” He adds that until recently, its prevalence was high only in Asia, where it remained sensitive to available antibiotics. “In recent years, cases have emerged showing this variant has acquired antibiotic resistance genes and has now spread globally. For this reason, the WHO issued an urgent call on this matter just before last summer.”

"The Vaccine Will Enter Its First Human Trials in 2025"

“Through vaccination, we can provide at-risk populations with enough immunity to stop the infection's progression without needing antibiotics or significantly reducing their use,” says Infante. This is where Vaxdyn’s K-Vax candidate comes into play. “The vaccine will enter its first human trials in 2025, having already undergone review by the European Medicines Agency regulators. It is designed to protect people undergoing invasive procedures in hospitals and, generally, neonates. Klebsiella kills 700,000 people per year and is the leading cause of neonatal sepsis deaths worldwide.”

Following efficacy testing in humans, the biotech company intends to partner with global-capacity pharmaceutical companies to target adults at risk worldwide. “With this profile and current incidence data, 320,000 deaths annually and 14 million disability days could be prevented, many from pneumonia,” says Infante. “The second approach will be vaccinating pregnant women so that maternal antibodies protect neonates against infection. A recent study shows that a Klebsiella vaccine administered alongside current tetanus campaigns for pregnant women in low-income countries could prevent 400,000 episodes of neonatal sepsis and 80,000 infant deaths each year.”

Vaxdyn has developed a technology that enables the creation of vaccines with “universal coverage.” “For technological simplicity, vaccines against Gram-negative bacteria like these typically aim to create immunity against a sugar on the bacteria’s surface, the so-called O-antigen. This sugar varies greatly among different Klebsiella pneumoniae variants, so these vaccines do not cover all variants worldwide or any future ones that are not yet accounted for in existing vaccines,” Infante explains. Vaxdyn’s technology, however, enables immunity targeting stable surface proteins called porins: “In our case, against two porins. We have demonstrated that the immunity generated targets all circulating types of Klebsiella globally and any future types, as these two porins remain constant. We use this same technology to develop vaccines against other bacteria, such as Pseudomonas aeruginosa. Our K-Vax candidate is being developed to prevent pneumonia caused by this bacterium, which is highly prevalent among people with cystic fibrosis or bronchiectasis.”

K-Vax has the support of CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), a consortium led by Boston University and funded by a global partnership. Vaxdyn is the first Spanish biotech company to receive CARB-X funding. “We have already accessed $5.5 million in non-repayable funds, with another $5.5 million potentially available,” Infante shares. “The European Commission happily joined this support last summer when we secured €14.5 million from the EIC Accelerator to fund clinical stages. CARB-X’s support also attracted our specialized investors, like the Portuguese fund Bionova Capital and the Fundación Botín’s Mind the Gap program. All of this is necessary to bring a vaccine to human clinical trials. Without it, development is not feasible. That is why Spain has traditionally not been a drug-developing country. It requires a significant capital investment. CARB-X has used $500 million since 2016 to support 100 projects in their early development phases,” he concludes.