Cannot test H5N1 vaccine on humans yet due to… procedures?

Professor Nguyen Thu Van, Director of Vaccine and Biological Products Company No. 1. Photo: LH

The public is eagerly awaiting the H5N1 vaccine; the government has also urged the Ministry of Health to expedite the research process to complete the H5N1 vaccine during several meetings discussing the prevention and control of avian influenza.

In an exchange with Professor Dr. Nguyen Thu Van, Director of Vaccine and Biological Products Company No. 1 – NIHE (VABIOTECH/NIHE), we discussed the reasons for the delay in human trials of the A/H5N1 influenza vaccine.

– NIHE is in the final stages of researching the H5N1 vaccine. However, it has not yet received permission for clinical trials on humans. Are there still obstacles?
– The institute is ready to conduct clinical trials on volunteers, but according to regulations, approval from the Ministry of Health is required. The Ministry of Health has requested to wait for the WHO’s response regarding the quality assessment of the vaccine batches sent to them, after which the procedures for clinical trial approval can proceed.

Meanwhile, WHO has advised that all documentation and legal procedures should be adequately prepared for submission to the relevant authorities for approval. If Vietnam requests, WHO will send experts to assist in evaluating these documents for the clinical trials.

On December 1, Professor Nguyen Van Dip and Professor Nguyen Thu Van held a meeting. Right after the meeting, Professor Dip affirmed: “I will promote this work so that Professor Nguyen Thu Van can clarify the unresolved issues before the evaluation council next week.”

In my opinion, WHO only assists us with technical expertise; they do not make decisions on our behalf regarding state management.

– This delay has caused many to express “doubts” about the process of researching and producing the H5N1 vaccine. Furthermore, there are reports that the Institute’s research proposal has been rejected?

That information is inaccurate. To be more precise, the research proposal has not yet been approved, and the scientific council has requested additional information for further clarification (I believe this is standard practice when reviewing a scientific research proposal).

Subsequently, there was a directive from the Ministry of Health and the Ministry of Science and Technology to wait for WHO’s feedback, hence the situation has not progressed until now.

If it had been rejected, why would we continue to research and wait? The technology proposal for producing the influenza vaccine that we submitted to the Ministry of Science and Technology is still quite new both domestically and internationally. Until now, global influenza vaccine manufacturers have used traditional technology, which involves production using SPF (Specific Pathogen Free) chicken embryos, while NIHE produces the A/H5N1 influenza vaccine using primary monkey kidney cells.

There are certainly many opinions surrounding this technological approach, but we remain persistent and hope for open and frank exchanges between scientists and managers so that all issues can be clarified, thus accelerating the research and production of the H5N1 influenza vaccine in Vietnam and promptly providing the community with the A/H5N1 vaccine.

Monkeys on Rieu Island, Quang Ninh, serving the research for the H5N1 vaccine

– There are opinions suggesting that the Ministry of Health is hesitant to allow the Institute to conduct clinical trials on volunteers due to the unclear origin of the virus. How do you explain this?

– I believe this opinion is inaccurate. In vaccine production, the strain of the virus is a prerequisite for success and is very important. We cannot conduct research without a clear origin of the vaccine virus strain.

The H5N1 vaccine strain that the Institute is using for the development of the A/H5N1 influenza vaccine was prepared at the National University of Tokyo, Japan, under the direct guidance of Professor Yoshihiro Kawaoka, a leading expert in reverse genetics who has been granted intellectual property (IP) rights for this technique.

The vaccine strain we are using has all the technical characteristics of the H5N1 vaccine strain provided by WHO (NIBRG-14) and shares the same origin as the wild H5N1 virus strain isolated from a Vietnamese patient, designated A/Vietnam/1194/2004 (H5N1), with the pathogenic gene segment removed. WHO, during their visit to work with the Institute in August 2005, after evaluating the documentation of the VABIOTECH/NIHE strain, clearly stated in their report that VABIOTECH has sufficient scientific experience and facilities to produce vaccines for human use.

Regarding the materials, VABIOTECH/NIHE uses primary monkey kidney cells, while if chicken embryos are used, they must be from “clean” chickens, meaning they should not carry specific pathogens (SPF). Moreover, the tests on monkeys to select clean monkeys have also been evaluated by WHO; not every monkey can be used for vaccine production; it must be a clean monkey. We have to exclude foreign agents from each monkey according to WHO’s technical guidelines on selecting clean monkeys for the production of live oral polio vaccines.

Scientists researching the vaccine at NIHE

– To date, how far has the Institute progressed in meeting WHO’s requirements?

– WHO has set out 9 requirements during the research and production of the vaccine, which include sending vaccine samples to WHO; checking the antigen content in the finished vaccine before clinical trials; preparing technical documents to send to the national testing center; submitting documentation for assessing foreign viruses in monkeys; writing a scientific paper on the ongoing research to publish in a reputable international journal; planning for potential large-scale production; regularly communicating with WHO regarding research activities (monthly); and if there are requests for assistance in evaluating documentation, WHO will provide help.

As of now, these requirements have been met. At this time, monthly meetings are held between WHO and the Institute.

– The Institute anticipated conducting clinical trials of the A/H5N1 influenza vaccine on humans in early 2006, but it seems this plan may not come to fruition…

– In principle, researchers cannot conduct clinical trials on their own volunteers because that would not be objective in self-assessing a vaccine they developed; they must contract with an authorized agency to carry out this work.

After receiving permission from the Ministry of Health for clinical trials and achieving favorable results from the trials, we will proceed with the product registration documentation before being granted circulation approval and officially entering production. This is a mandatory process for any newly developed vaccine.

However, the Institute has fully prepared the number of volunteers for clinical trials. The first batch consists of about 20 individuals, and the second batch is 250 individuals. These participants are aged between 18 and 45, meeting all selection criteria, and are completely healthy, with no contact with infected poultry or residing in outbreak areas.

– This means everything has been fully prepared; we are just waiting for the decision to conduct clinical trials on humans?

– That’s correct. However, this is not the right time to conduct field experiments as we are currently at the peak of the outbreak; and if the situation is urgent, we must proceed with utmost caution. The testing will take place at an appropriate time. At this pace, it will likely be until the end of 2006 before all processes are completed.

– Thank you, Professor!

Lệ Hà (interviewer)