Merck’s Adenovirus Mis-adventure, 2007

Merck’s Adenovirus Misadventure.

Merck is the biggest developer of Vaccines. It is also a pioneer in harnessing Adenoviruses to transfer genetic material into human cells. Today, we have more than a couple of vaccines that uses an adenovirus vector for covid-19 vaccine. But Merck has none. Why ? 

The story of modern day vaccines began in 1796 when Dr. Edward Jenner inoculated 9-year-old James Phipps with cowpox as a way to protect him from smallpox.

Eight decades after Jenner, Louis Pasteur developed the first live attenuated bacterial vaccine. Viruses were unknown then. Credit must go to Louis Pasteur for formulating the Rabies vaccine in 1885. 

By the 1950s we had been able to identify viruses, grown them in cell culture and developed Polio vaccine both live attenuated and killed vaccines. Then Merck took over.

Between 1957 to 1984 Dr. Maurice Hilleman of Merck had developed more than 40 human and animal vaccines : Measles, Mumps, Hepatitis A and B, Chickenpox, Meningitis, and Pneumonia.

Yet Merck had not joined the race for Covid Vaccine. Is it not surprising.

In 1998, Merck started an ambitious program of developing a vaccine against HIV. It had pumped billion dollars in developing a totally different platform for vaccine development :- An Adenovirus vector platform.

Till such time, we are using a whole virus either killed or a live attenuated one against Small pox, Chicken Pox, Polio etc. Scientists were thinking, is it possible to use a mild virus to carry the genetic material of a lethal one into human body without harming the body ? A courier system.

Viruses are natural carrier of genetic material. Every virus is fitted with two equipment- One a spike protein that helps it to get inside a cell by attaching to a receptor. Then the virus injects its genetic content inside the cell.

Merck had chosen the Adenoviruses virus type 5. AD5. Before that it had explored other types like a chimpanzee one, AD26 and discarded to zero on the AD5.

Adenovirus is a DNA virus. It was first isolated from the adenoid gland of a sore throat patient. It can infect every cell type in our body. It can efficiently deliver its DNA material into the high security nucleus of a cell.

It is also roomy. It has enough space at its core in which scientists can put a gene of their interest. The virus will carry the payload and deliver inside the nucleus of the target.

After a successful decade of research in monkeys and other lab animals, Merck had gone ahead with Phase II  human trial in 2007. It is conducted in the sub Saharan Africa and is known as the STEP trial . It was followed by Phambilli trial in South Africa.

It was the most unfortunate trials in the history of vaccine development. On September 21 2007, the preliminary findings suggested that this vaccine did not reduce the disease.

The results were confirmed later on,”…actually increased the chances of getting HIV among the vaccinated.”

It was an anti climax.

Today we know the reason for such paradoxical result. it is called the Antibody Dependent Enhancement (ADE). In Dengue fever, antibodies may increase the infection instead of protecting against the virus. But back in 2007, this enhancement could not be explained,The trial was quickly aborted. 

This also killed the future of AD5 vector, and Merck’s billion dollar initiative was reduced to ash.

Till date, Merck has not recovered from the hit. It never developed a vaccine against Covid-19. Though it came up with an oral drug: Molnupiravir.

Incidentally, today we have two successful vaccines that uses the discarded platform of Merck: Covishield uses the Chimp Adenoviruses virus and Janssen uses the AD 26 platform.

Merck uses none.