There are at least two dengue vaccines (Denvaxia and Qudenga) in commercial production and in use worldwide. In addition to this, the vaccine that you have worked with TV-005 is undergoing trials in different countries. Why did you choose this vaccine to test?
Rashidul Haque: icddr,b has collaborated with investigators from the US National Institutes of Health and The University of Vermont and Johns Hopkins University. These US collaborators have been studying this vaccine since it was developed; they have performed multiple earlier studies with this vaccine. In addition to experience with this dengue vaccine and clinical trials, our collaborators at the University of Vermont also have a long history of working with the icddr,b on other studies (since 2002). Together, it was a logical choice to study TV005 at the icddr,b.
You have completed the second phase trial of TV-005 vaccine. May I ask you the results of this trial?
Rashidul Haque: This trial was designed to test safety and immune responses (a phase 2 trial), from young children to adults. It was well tolerated by all subjects and prompted an immune response to all serotypes of dengue. This trial was not designed to be large enough to show if the vaccine prevents dengue (it was not a phase 3 efficacy trial).
The number of people you have administered this vaccine is negligible. This is a shortcoming of this trial, as you acknowledge in your paper. But can it be said that the vaccine has been successfully tested?
Prof Beth Kirkpatrick: Phase two trials are designed to be small since there is so much attention to safety and immune responses. Each volunteer is carefully observed since safety is of paramount importance before we proceed to larger trials. Note that if the vaccine had been unsafe, we would not want to exposure many people to it. This is not the end of the study of this vaccine.
The study done by the iccdr,b used TV005 vaccine manufactured by the US National Institutes of Health, who will only support small, early phase 1 and 2 trials of vaccines designed by their scientists. Larger trials must performed in partnership with pharmaceutical companies, and must use the vaccine manufactured by that pharmaceutical company.
Also, note that since the US NIH is not a pharmaceutical company, and it permits licensure of its vaccine by many pharmaceutical companies. This means that this vaccine could be made across the world by multiple pharmaceutical companies. Already many companies have licensed this vaccine and others are in the process of licensing this vaccine- including Bhutantan (Brazil), Merck (USA), Serum Institute (India), Panacea Biotech (India) and others.
Trials of this vaccine (TV-005) are also underway in other countries of the world. What are their similarities or differences with the results obtained in Bangladesh?
Prof Beth Kirkpatrick: Thus far, there are no obvious differences in response to this vaccine by geographic region, which is good news since data from other locations can be compiled.
The vaccine produced antibodies against all four types of dengue. What is the significance of this? Is this the only vaccine that has produced four moderate levels of antibodies?
Prof Beth Kirkpatrick: The ideal dengue vaccine has strong immune responses to all four serotypes of dengue, which reflects a good chance that the vaccine will prevent people from illness caused by all four serotypes of dengue. This vaccine seems to give similar antibody levels to all four serotypes. The other two vaccines produce antibodies to all four serotypes but are heavily concentrated to one serotype (Dengvaxia to Dengue 4 and QDenga to Dengue 2).
I heard that the third phase trial of the vaccine has been done. Can you say something about its results?
Prof Beth Kirkpatrick: One phase 3 trial is partially done, in Brazil. Each pharmaceutical company will have to do their own phase 3 trial.
During the Brazil trial, only Dengue 1 and 2 were circulating, so efficacy data is only available for Dengue 1 and 2 (which is about 80% in all ages); this is the strongest efficacy data so far for any dengue vaccine. However, we do not have data on Dengue 3 and 4 yet.
Merck is planning another phase 3 trial at multiple sites in the IndoPacific region.
Panacea Biotech is planning a phase 3 trial at multiple sites in India.
How effective are the vaccines that are now commercially available?
Prof Beth Kirkpatrick: The two vaccines now available in different areas are Dengvaxia (Sanofi) and QDenga (Takeda). Very briefly, both are very good for individuals who have already experienced at least one dengue infection. Both have concerns of not covering all serotypes. This is a concern for persons who have never had dengue, many of whom are children.
As you know, in the Phillipines, use of Dengvaxia was associated with more hospitalizations from dengue in vaccinated children. Thus, use of this vaccine is now permitted only after a person is tested and shown to have past exposure to dengue and not recommended otherwise.
Qdengue is newer and is very strong against Dengue 2, but it appears it is weak against the Dengue 3 component, and there is not a lot of information on dengue 4.
When will the third phase trial of TV-005 vaccine take place in Bangladesh? What preparation is required for this?
Rashidul Haque: Partnership with a pharmaceutical company will be required. It may not be necessary to perform the phase 3 trial in Bangladesh if data from elsewhere is acceptable to the government of Bangladesh. Many discussions are ongoing to determine if and how Bangladesh might participate in the further testing of this vaccine.
9. After the vaccine was developed and it underwent successful trials, the matter of price comes to the fore. A few companies have received approval to market the TV-005 vaccine in India and Vietnam. How far will the TV-005 vaccine be affordable given our country's socio-economic condition?
Dr Rashidul Haque: The cost of the vaccine will be stipulated by the pharmaceutical company in negotiation with whomever wants to buy it. Presumably, if there are many millions of doses ordered each year, the cost will be lower.
People are very interested in the dengue vaccination. When can we get the TV-005 vaccine?
Prof Beth Kirkpatrick: We must wait until one of the pharmaceutical companies licenses the vaccine. Then the Bangladesh government will decide it if appropriate for Bangladesh.
Can the country where the vaccine trial takes place receive special discounts on vaccine availability and cost? Will we have such a benefit?
Rashidul Haque: We do not know if this is possible. Presumably, this would require negotiations between the government and the pharmaceutical company.
Bangladesh is a vaccine ‘champion’ country. We saw this in the case of the corona vaccine. As scientists, could you have a role in ending the vaccine's monopoly when it is commercially produced? Can you take on that responsibility?
Dr Rashidul Haque: Bangladesh is to be congratulated for its great work on COVID-19 vaccines! As scientists, we will advocate for the best vaccine first, and then together we must work with government and industry partners to make sure all vaccines are inexpensive, especially for people who cannot afford them.