AU study seeks to understand antibody survival and vaccine longevity

Recent announcements from Pfizer and Moderna about what appear to be highly effective vaccines against the virus that causes COVID-19 have generated a lot of headlines and excitement. But what is still unanswered is how long that protection would last.

That is the focus of Dr. Nagenda Singh, an immunologist at Augusta University, funded by a recent $2.5 million grant from the National Institutes of Health.

Research has already shown that antibodies against the virus can fade within weeks in some who have recovered, particularly those who did not have a severe infection. Another study at AU is focused on front-line workers and whether those who have already been infected can be reinfected.

But this actually goes back many, many years, Singh said.

“This important question has been going on for many years, not just in the last six months or one year,” he said.

For instance, most people only need to get the measles, mumps and rubella vaccine once in a lifetime, whereas others need to be repeated every five to 10 years, Singh said.

“The reason is the antibodies made by these vaccines only last for five to 10 years,” he said, whereas the MMR antibodies “last almost all of our lives.”

With flu shots, the antibodies are probably good for only a year, Singh said.

The difference is in the lifetimes of the cells that make those antibodies, Singh said. Put simply, B cells in the immune system encounter a pathogen like the virus or influenza and become plasma cells that produce antibodies against that pathogen. Those plasma cells then home to the bone marrow.

“These cells are the factories that make the antibody,” Singh said. “As long as the plasma cells live, the antibodies live in the blood.” Once the plasma cell dies, however, the antibody level drops and protection wanes, he said.

“We don’t know what makes some plasma cells live much, much longer than others,” Singh said. “That’s the most important central question.”

One thing that appears to be important for plasma cells is getting into the bone marrow, he said.

“If they don’t get to the bone marrow, they are extremely short-lived,” Singh said. “Once they reach the bone marrow, this process of longevity starts.”

But what happens inside the bone marrow is also not clear, Singh said.

“Once they reach the bone marrow, what happens to them is still a mystery,” he said.

Singh has identified a key pathway and molecules that are necessary for the plasma cells to form and perhaps to survive. His lab is taking two different approaches.

One is blocking key elements of the pathway in mice and infecting them with influenza to see whether they form the influenza-specific plasma cells. The other approach is infecting the mice and allowing specific plasma cells to form, then blocking the key molecules to see how long the plasma cells and antibodies survive.

“If we can understand this, we can make the vaccines that will induce plasma cells that can live, instead of one year, 10 years, 20 years or 50 years so we have to take those vaccines only once in our lifetimes,” Singh said.