“There is no evidence that mAb or vaccine are effective in a confirmed NiV infected person”

August 7, 2019 0 By S Harachand

Dr Christopher Broder is Professor and Chair of the Department of Microbiology at Uniformed Services University of the Health Sciences (USU), United States Department of Defence. A collaborative group led by Dr Broder published a ground-breaking discovery that paved the way for the two most promising countermeasures against Nipah and Hendra viruses: A soluble G-protein vaccine for potential human-use and m102.4 — a monoclonal antibody as an effective therapy against both viruses. These are both in development for use in humans. Edited excerpts from an interview:

It has been reported that mAb m102.4 is showing highly promising results in NiV infection treatment in humans. What is the current status of the pre-clinical studies of the antibody?

It is a human monoclonal antibody called m102.4. It binds to a specific protein (G protein) on the virus or virus-infected cell. It neutralises the virus and prevents the virus from infecting more cells. It is also effective against Nipah’s sister virus, Hendra virus in Australia. We decided some years ago in 2005 to isolate human anti-Nipah / Hendra antibodies to the Nipah/Hendra the vaccine we made in 2001. The vaccine is soluble G protein, so we used it to identify and isolate m102.4 (the human antibody). We wanted to develop a therapy (the antibody) for Nipah and Hendra infection. This is called passive immunization.

In our animal studies, the antibody helps the subject fight the virus infection. Together, the antibody — if given early enough — and the subject’s natural immune response to the virus infection will allow full recovery.

However, it has never been given to a confirmed Nipah infected and sick individual. In all cases in Australia, the antibody was given immediately upon a known exposure to possible infection and before illness (post-exposure prophylaxis). We do not have evidence in people that it is effective in an already sick person; it has never been done. We, of course, hope that it might. 

The m102.4 antibody has completed a Phase I safety trial in humans in Australia successfully. A report of the trial is in the process of being submitted for publication.

 

What were the findings when m102 was tried in humans on ‘compassionate use’?

We gave the cell line that makes the antibody (for free) to Queensland Australia and they are producing it there for compassionate use. The antibody produced in Australia was also used in a Phase I human safety trial. We are now in the process of giving the cell line that produces the antibody to the Serum Institute and ICMR in India (for free), so that India can make their own antibody drug in the country and not have to source it from Australia.

It has been given to 14 people in total, 13 in Australia and 1 in the United States. In all cases no serious adverse reactions occurred. In all these cases, it was given before any signs of illness. It was administered because of a risk of infection exposure.

 

Recently, there have been NiV outbreaks in certain regions of India, probably with NiV Bangladesh strain of the virus. Has the m102.4 or Hendra-sG subunit vaccine been tested in NiV-B strain?

Yes, both the mAb (m102.4) and the Hendra-sG vaccine have been tested against NiV-B in animal models (ferrets and monkeys) and both are effective. However, the studies indicate that the mAb, needs to be given early, before a serious onset of the disease. Still, the Hendra-sG vaccine is equally effective in providing total protection from infection and disease in monkeys and ferrets against Hendra virus, Nipah-Malaysia virus and Nipah-Bangladesh virus.

 

How effective is Hendra-sG vaccine as a prophylactic in humans?

We do not know. We expect to test the immune response to Hendra-sG vaccine soon in people in a Phase I trial.

 

Is there any potential therapeutic specific to NiV in development?

Specific for just Nipah? Not that I am aware of. All the vaccines and countermeasures we are developing are aimed at being effective against all 3 known pathogenic henipaviruses.