January 14, 2020
Happy New Year! On behalf of all of us at the Lupus Research Alliance (LRA), thank you so much for your kindness and generosity in 2020 and prior years.
2021 starts off with some exciting milestones for the lupus community including a new treatment for lupus nephritis. But Recently, our Trustees approved a $3 million project to explore the use of these vaccines specifically for people with lupus. This is a significant expenditure for LRA, but because many of the COVID-19 vaccines under development utilize brand new technology, assessing how the new vaccine platforms might impact people with lupus is very important and timely.
The reason these new vaccines have been developed, tested, and deployed so rapidly is because they produce immunity very differently from traditional vaccines. Older vaccines use dead or severely attenuated (weakened) viruses to provide active immunity. Fortunately, these new vaccine technologies became readily available just as the COVID-19 crisis hit. The critical question for us is, which new vaccine will be most appropriate for lupus patients?
To address this question, the LRA recently convened a meeting attended by experts in vaccinology, immunology, and rheumatology as well as representatives from the LRA Research Committee, the National Institutes of Health (NIH), and the American College of Rheumatology. While our expert advisors felt that all of the vaccines would probably be safe and effective for those with lupus, the absence of data made it impossible to be 100 percent certain. Some vaccines may prove more appropriate for people with lupus than others. However, we will only know with in-depth study. It is for precisely this reason that LRA will be committing so much time, funding, and effort to provide answers to people with lupus.
Many of the new vaccines use the spike protein to stimulate the immune system. Spike protein decorates the surface of all coronaviruses including SARS-CoV-2. Think of spike protein as a key which unlocks a portal called the ACE2 receptor on the surface of human cells and allows genetic material from the virus to penetrate the cell. Once inside, the genetic material of the virus hijacks the machinery of the cell to produce copies of the virus; that is what makes you sick.
Many companies developing these new vaccines use just the spike protein to stimulate the immune system to remember how to fight if faced with the actual virus in the future. The Pfizer and Moderna vaccines use the blueprint within messenger RNA (mRNA) to instruct cells to manufacture spike protein. Once the cells are taught by mRNA to produce spike protein, the cells of inoculated people produce enough of it for the immune system to remember and recognize it as an invader and neutralize the virus, preventing the person from becoming ill.
The AstraZeneca and Johnson and Johnson (Janssen) vaccines use a different approach to achieve the same ends. Their vaccines fuse the genetic instructions for producing spike protein to a harmless adenovirus that can invade cells but doesn’t cause disease in humans. Like a long-haul trucker dropping off his cargo, the adenovirus drops off these genetic instructions which teach cells to make spike protein. As with the mRNA vaccines, the spike protein inspires the immune system to memorize how to destroy the SARS-CoV-2 virus on sight.
The third new vaccine platform that Novavax, and Sanofi with GSK are developing works by directly injecting synthetic spike protein. While this type of vaccine may elicit a less robust immune response than the others, the developers get around this by pairing their vaccines with a chemical called an adjuvant. Adjuvants are substances that incite the immune system to be hypervigilant and may inspire long-lasting immune response.
Unfortunately, no one knows how these technologies may impact lupus. Some experts speculate that the mRNA vaccines might induce production of interferons which are already elevated in many lupus patients, making us wonder if that could cause a flare. The protein vaccines are paired with adjuvants to boost the immune response — which may or may not be an issue for people with lupus. The best guess is that none of this will turn out to be a problem, but it is important to find out for sure. Our new project will not provide answers in time for patients to determine which vaccine might be best for them. Patients will need to make decisions in consultation with their rheumatologists.
So, why evaluate these new vaccine platforms? First, much like the flu, SARS-CoV-2 may turn out to be endemic — meaning they would be permanently found in human populations. If this occurs and if the durability of vaccine protection turns out to be relatively short, it may be necessary to repeat the vaccinations periodically. Secondly, these new vaccine platforms will likely be used for other vaccines in the future. In the fullness of time, we should be able to advise people with lupus which forms of the vaccine are most appropriate for them, especially if patients need to be re-vaccinated year after year.
We are asking the NIH and industry partners as well as our lupus community to join us in this important endeavor, and we’ll keep you posted on our progress.
Meanwhile, if you haven’t seen it yet, I encourage you to watch our Vaccines and Lupus: What to Know Amid COVID-19 video series where I discuss the role of vaccines, the new COVID-19 vaccine technologies and in the latest Episode 3, what we’re doing to evaluate the new technologies in our lupus population. I am also happy to answer your questions about any of this.
With warm regards,
Kenneth M. Farber
President & CEO
Lupus Research Alliance