Thai Doctors Pioneer Next-Gen Pertussis (Whooping Cough) Vaccine: Fewer Doses, Full Protection for Vulnerable Patients” 

The Faculty of Medicine, Chulalongkorn University, conducted a study to develop a new generation of Pertussis vaccine (recombinant pertussis vaccine) with a reduced dose from 5 μg down to 2 μg of genetically detoxified recombinant pertussis toxin, to maintain immune efficacy at a more affordable price for vulnerable populations to ensure equal access and coverage for the population.
When was the last time you had the pertussis (whooping cough) vaccine? 

Many people may not even remember how many and the last time they received vaccinations. They may also believe that once they are vaccinated during childhood, there is no need for another shot because immunity can last a lifetime. And whooping cough is under control, and new cases are barely found in countries where successful pediatric immunization was established.

In fact, the pertussis vaccine can create immunity for 3-5 years after vaccination, and the disease is still around. The latest data from the Department of Disease Control, Ministry of Public Health, Thailand, revealed that in the outbreak of pertussis in 2024, there were 1,186 whooping cough cases, representing 44.74 cases per 100,000 people. Of these, there were two deaths. The age group that saw the highest cases was 0 – 4-year-olds, totaling 818 cases, followed by the 5 – 9-year-olds, totaling 159 cases, and 10 – 14-year-olds, totaling 59 cases. These numbers are higher than the standard value for the past 5 years.

Vaccination is therefore important, especially in pregnant women, adolescents, and adults with chronic medical illnesses, as whooping cough is a highly contagious and life-threatening respiratory infection, especially if it occurs in young infant.

Currently, there are both the previous generation of vaccines (acellular pertussis vaccines) imported from abroad and newer recombinant pertussis vaccines invented by Thai companies and produced locally.  But these vaccines are at a relatively high price, and not affordable to many people.  Therefore, the Thai medical team from the Faculty of Medicine, Chulalongkorn University has invented a “new generation of recombinant pertussis vaccine, at a reduced dose from 5 µg to 2 µg of genetically detoxified recombinant pertussis toxin to make the vaccine cheaper for the Thai population at risk, to ensure maximum reach to these people.

“The number of whooping cough cases may be underreported because doctors often overlook the symptoms and fail to diagnose the disease,” said Professor Terapong Tantawichien, MD, an infectious disease specialist at the Faculty of Medicine, Chulalongkorn University, and head of the new-generation pertussis research team. 

“Whooping coughs is a rare disease. Doctors may not even think about it, and don’t prescribe a screening test because the cost of the PCR (Polymerase Chain Reaction) test is high.” 

“According to international data, the global diagnosis rate is significantly lower than reality. For every single case detected, it may in fact represent one in a hundred or even one in a thousand actual cases, meaning the true situation is likely being underestimated.” 

Whooping cough is not an Emerging Infectious Diseases (EID), but it has always been with humanity because it is caused by a bacterium called Bordetella Pertussis, which is present in humans.  In Thailand. People used to call it a “100-day cough”.

“Infants and children with this disease suffer violent coughing fits until they turn green, then they vomit and die. In adults, chronic coughing lasts for months and interferes with everyday life. Other symptoms include vomiting, aspiration, insomnia, broken ribs because of the coughing, and exacerbations of asthma or chronic obstructive pulmonary disease (COPD).” Prof. Dr. Terapong said. 

“Whooping cough is an infection caused by the sputum that comes out with the cough. Coughing fits that last over 2 months are extremely contagious. One patient can have up to a 30-50 percent chance of infecting other people they come in contact with.”

Fifty years ago, a whooping cough was a significant public health problem due to the high number of cases in both children and adults. Until 30 – 40 years ago, many countries, including Thailand, began vaccinating young children against whooping cough, resulting in a lower mortality rate since then. 

However, 25 years ago (2000), after the carpet vaccination, whooping cough cases in adults started to be found.

Around 2013, the Infectious Diseases Research Group, Department of Medicine, Faculty of Medicine, Chulalongkorn University began studying adults with chronic coughing that was not cured for more than 3 weeks and diagnosed with “acute bronchitis”.

“We found that 1.3% of adult patients with more than 2 weeks chronic cough had pertussis (whooping cough)!” Dr. Terapong added that the findings made the Chulalongkorn medical team go back to look at the cases of babies aged between 1 and 3 years old suffering from a series of coughs and found them to have whooping coughs as well. 

“We studied the reason for what happened and found that whooping cough is hard to diagnose. Bordetella pertussis culture is also very difficult. Currently, it has to be screened with the expensive PCR method to look at molecular sources, and it cannot be tested anywhere. When we did the research in 2013, we had to Ask for help from the Ministry of Health, Thailand, to find that whooping cough still exists in children and adults. This is like foreign countries where the disease still exists, but no one knows because there has been no definite diagnosis. During the past 10 years, the European Union has turned its attention back to whooping cough.” Prof. Dr. Terapong said. 

The Ministry of Health provides free whooping cough vaccination for infant, younger children and pregnant women at state health facilities nationwide. For babies and toddlers, a series of 5 combination doses to prevent diphtheria-tetanus-whooping cough is given at the ages of 2, 4, 6, and 18 months, and a booster shot at the age of 4-6 years old. For pregnant women, the whooping cough vaccine is given during weeks 27-36 of the pregnancy.

However, the acellular pertussis vaccine has the longest protection for 3-5 years, so doctors recommend that adolescents and adults get a booster shot every 10 years, which is at the public’s expense.

Currently, the pertussis vaccine for children of 7 and above and for adults is both imported (acellular pertussis vaccines) and produced domestically (recombinant pertussis vaccine). The price is high, especially for vulnerable groups who may have difficulty accessing the vaccine. The Chulalongkorn University Faculty of Medicine has therefore invented a vaccine that is as effective, but in a smaller dose, to bring down the price.

Prof. Dr. Terapong, M.D., distinguished the older and newer vaccines as follows: 

“Immunity from older vaccines lasts only 2-3 years, while diphtheria and tetanus last 10 – 20 years,” Prof. Dr. Terapong said. 

The new generation of pertussis vaccine as recombinant pertussis toxin was developed by BioNet-Asia Co., Ltd., a Thai company. The vaccine comes in two types: 

“A new generation of vaccines for pregnant women, at-risk adolescents, adults and elderly with underlying diseases uses a new manufacturing process called Recombinant Protein by introducing the Bordetella Pertussis gene into other bacteria and allowing other bacteria to make immune-building proteins. The structure of the protein is not compromised by chemicals. Immune tests are higher and last longer because the protein shape generated from other bacteria is not distorted.” Dr. Terapong explains the production process of the next generation of vaccines.

“Vaccination in pregnant women helps transfer specific immunity to the baby. Infants under 2 months of age receive maternal antibodies through the mother’s vaccination. After 2 months, when the baby begins receiving pertussis vaccinations, they can start building their own immunity—for example, after just 2 doses, the infants will already have protection in their early life. In addition, a single pertussis vaccine is still necessary for pregnant women who have back-to-back pregnancies, because getting the combined diphtheria-tetanus-pertussis (TdaP) vaccine may result in excessive doses of diphtheria and tetanus vaccines.”

The new production process of pertussis vaccine using the recombinant protein method has been in operation for 10 years but has only been commercially available in the past 3-4 years. The 5-mcg pertussis vaccine is priced at 700 – 800 baht per dose, which is still expensive for many groups of the population. So, Dr. Terapong and the vaccine research team came up with the idea to make vaccines cheaper, more effective, and safer.

“To provide this vaccine for free for Thai pregnant women and adolescents, the price of the vaccine must be low. Expensive TdaP or aP vaccines of 5 µg are already good. They give immunity for at least 5 years, but the dose may be too large.” 

The Chulalongkorn University research team requested funding from the government to support the research project and worked with a private company (Bionet-Asia) in reducing the dose of the Recombinant Pertussis vaccine from 5 μg to 2 μg of genetically detoxified recombinant pertussis toxin to make it cheaper while maintaining the efficacy.

“The study found that reducing the dosage does not decrease immunity and does not compromise the ability to generate an immune response for protection. The side effects, when compared to older vaccines and higher dose recombinant pertussis vaccines commonly available on the market, were not different—if anything, they appeared to be even fewer. The side effects mentioned include pain, swelling, and redness at the injection site, similar to those of typical vaccinations.” Prof. Dr. Terapong said. 

There are two types of the new reduced-dose pertussis vaccine: 

“Number 2 refers to the 2-microgram vaccine dosage. Currently, Boostagen 2 has already been registered, while Pertagen 2 is still awaiting registration. It is expected to be produced and available on the market within the next two years. The price has not yet been determined, but we will ensure it is cheaper than the pertussis vaccines currently being sold.” 

Prof. “Dr. Terapong hopes that once this vaccine becomes more affordable, the government will consider purchasing it to support vaccination for pregnant women, adolescents, and adults with underlying health conditions.”

“When the vaccine becomes more affordable, we hope the government will consider purchasing it, as it is a vaccine whose research has been supported by the state. At the same time, Bionet-Asia will also benefit by being able to export this vaccine to international markets such European countries and Asia.” 

Prof. Dr. Terapong said that EU countries are now considering importing the new, recombinant pertussis vaccines from Thailand. 

“It is a point of pride that other countries are considering importing this group of vaccines. For example, the EU countries are reviewing the new recombinant pertussis vaccine for potential use. If approved, it would be the first vaccine researched and produced by Thais to be used in Europe. In addition, India and Singapore have also expressed interest in importing vaccines from Thailand.” 

The current pertussis (whooping cough) vaccine prevents the disease reasonably well. The results of the pertussis vaccination in pregnant women showed a 90% decrease in whooping cough in infant, but the problem is that the immunity does not last long.

“Older pertussis vaccines from abroad typically protect for 2–3 years. The current Thai-produced vaccine lasts for 5 years, but whether it could extend to 10 years remains unknown. If it does reach 10 years, the diphtheria-pertussis-tetanus vaccine could potentially offer protection over the same period.” 

Extending vaccine protection to 10 years is the next major goal for the medical team at Chulalongkorn University.

“Vaccine production using the recombinant protein method is already effective, but the question is how to make immunity higher and last longer. For example, should adjuvants be added, should higher doses be used, or are booster shots necessary? These are the approaches to explore in the future.” 

Finally, Prof. Dr. Terapong emphasized the importance of pertussis vaccination: “Pertussis (whooping cough) is a disease that many thoughts had disappeared, but it still exists. For the new recombinant pertussis vaccine, current data show that immunity lasts at least 5 years. For those who have already received the combined diphtheria-tetanus-pertussis (DTP) vaccine, immunity to diphtheria and tetanus can last up to 10 years. It is recommended to receive a separate pertussis vaccine. Pregnant women who have already received the combined vaccine and become pregnant again should also receive only the pertussis vaccine for protection of pertussis in infant.’”