I take Ocrevus, and if there's less of an antibody response to the Covid vaccine because of this, will a third shot make a difference?

Here is My Question:
I take Ocrevus, and if there's less of an antibody response to the Covid vaccine because of this, will a third shot make a difference?

Answer:
Vaccine responses are complicated and depend on many environmental (such as exposure to B cell depleting agents like Ocrelizumab, rituximab and ofatumumab to name a few) and intrinsic factors (such as age, genetics).  One hypothesis is that the effectiveness of a vaccine response results from a race between the reactivation of immune memory and the spread of the virus after exposure. Now this is where it gets a little complicated, so I will try to simplify things.

B cells ( the cells destroyed by Ocrevus, rituximab and ofatumumab )are essential for early vaccine effectiveness, particularly against viruses and other pathogens that are outside of your cells and spreading throughout the body early in an infection ( so call incubation phase).  Some B cells turn into plasma cells after vaccination. Only plasma cells produce the antibodies that halt the initial spread of a viral infection. T cells are essential for destroying pathogens inside of cells or an established infection. Therefore, T cells are more important later in the stage of viral infection. Both cell types work together to create a maximal and rapid response. 

Interestingly, the plasma cells, that produce the antibodies measured in blood tests which check for your immunity against viruses, are not destroyed by Ocrevus and other medications that target the CD20 protein. This is because Plasma cells do not express CD20 on their cell surface. Unfortunately, plasma cells created by an initial vaccination (what is called priming) are short lived. This is one reason you typically need a second vaccine shot.

So, it is reasonable to expect that medications depleting circulating B cells will decrease vaccine associated antibody responses. How much this happens will depend on how long you've been receiving the B cell depleting drug and how recently you've received a dose, as well as many other factors such as your age. The end result is that antibody responses to a vaccine, the type of response required for early elimination of the virus after exposure, will be lower and it will be more difficult for people exposed to the virus to clear an infection rapidly. This is possibly one of the reasons that immunosuppressed people do not clear the COVID19 virus rapidly and may spread the infection to other people for a longer period of time. How much B cell depletion will affect T cell responses to the virus, the responses required to combat an active infection after it is established and you are sick, is still unclear and being sorted out.  We suspect that diminished vaccine responses will require some people receiving B cell depleting therapies to receive subsequent booster vaccines in the future. Stay tuned for more information.

Revere P (Rip) Kinkel, MD
​Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego