COVID-19 update: Vaccines & treatment options

As the pandemic wears on, pressing questions emanate from the primary immunodeficiency community. How does COVID-19 affect a person with PI? What COVID-19 vaccines are recommended for a person with PI? Can a person with PI actually create antibodies to the vaccine?

Dr. Mark Ballow, a member of IDF’s Physician Advisory Committee and an allergist-immunologist in the Division of Allergy & Immunology at the University of South Florida, and Dr. Jolan Walter, division chief of the University of South Florida (USF) and Johns Hopkins All Children’s Pediatric Allergy & Immunology Programs, addressed those questions and more at a January 21 IDF Forum, “COVID-19 Update & Treatment Options.”

The presentation covered topics including:

• Status of COVID-19 in the U.S. and worldwide
• Vaccines available now and in trials
• How the vaccines work
• Common questions about COVID-19 and vaccines
• Recent studies on how COVID-19 affects both adults and children with PI

With more than 400,000 deaths and 25 million cases in the U.S., COVID-19 shows no signs of stopping in its spread. To complicate matters, new virus variances in the U.K., South Africa, and Brazil appear to be more contagious.

Still, scientists continue to research the development of vaccines. The following is an overview of the number of vaccines in various trials:

• Phase 1 – 41 vaccines testing safety and dosage
• Phase 2 – 22 vaccines in expanded safety trials
• Phase 3 – 20 vaccines in large-scale efficacy tests
• Limited – 8 vaccines in early or limited use
• Approved – 2 vaccines approved for full use

The two vaccines currently available to those living in the U.S. are made by Pfizer-BioNTech and Moderna. Both are mRNA vaccines, which means they are not live vaccines, but rather mRNA packaged in oily bubbles or lipid nano-particles. When they are administered, the lipid nanoparticles get inside the cell, the mRNA is translated into the spike protein, and then gets out of the cell, and the immune system then makes not only an antibody response, but also a cellular immune response, or T cell response.

The Pfizer vaccine has an efficacy rate of 95% and is a muscle injection which requires two doses injected three weeks apart. The vaccine’s storage temperature is -94 F, which requires special facilities and is thus difficult to store.

The Moderna vaccine has an efficacy rate of 94.5% and is a muscle injection that requires two doses injected four weeks apart. Moderna is easier to store - and thus distribute - because it can be kept in refrigeration for 30 days or at -4 F for six months.

In addition to the Pfizer and Moderna vaccines, another vaccine that may be available soon is the Oxford-AstraZeneca vaccine. Produced in the U.K., this vaccine is also based on the virus’s genetic instructions for building the spike protein.

However, unlike the Pfizer and Moderna vaccines, which store the instructions in single-stranded RNA, the Oxford vaccine uses double-stranded DNA. The DNA from the spike protein genome is packaged in a vector and delivered.

“The AstraZeneca is a little bit different. In this case, you’re using the DNA from the virus, particularly the sequences related to the spike protein. Remember, the spike protein attaches to the cell in order for the virus to gain entry into the cell,” explained Dr. Ballow.

“So this particular DNA is packaged into an adenovirus, the kind that causes the common cold or flu. This type of adenovirus used to package the DNA is an unusual virus that actually comes from a chimpanzee, not from humans. It can’t really infect us because the guts of the virus do not exist inside the package, just the DNA of the COVID-19 virus.

“Similarly, once it’s injected and gets inside the cell, the DNA is unpackaged, transcribed into mRNA, and the mRNA is translated into a spike protein, which then we make an immune response to.”

Dr. Ballow said the AstraZeneca vaccine might come before the FDA by the end of January or early part of February.

Another vaccine under research is the Novavax vaccine, produced by a Maryland-based company of the same name. The vaccine is protein-based and a bit different than the others discussed.

“They package the spike protein and deliver it with an adjuvant, which boosts the immune system - so that we make a really good response, both humoral and cellular,” explained Dr. Ballow. “Unlike some of the others, this may require only one injection, and not two.”

The Novavax vaccine is still in clinical trials but it may come before the FDA in March or April, depending on the amount of time it takes to get through phase 3 trials.

With the two vaccines on the market in the U.S. now - and others on the horizon, persons with PI may be asking, should I get the COVID-19? While there is no data on how effective the vaccine is for persons with PI, said Dr. Ballow, the global consensus is that persons with PI should receive a vaccine, except within rare subgroups.

“The opinion by experts throughout the world is that we should give our patients the vaccine. We know they’re not going to respond as well as the general population, but even if they make some antibodies and if they make a cellular immune response, we think that’s great. Therefore, the general recommendation is to give these vaccines,” said Dr. Ballow.

Delving even further into the topic of immune response to the vaccine by persons with PI, Dr. Ballow used the flu vaccine as an example. He said that many persons with PI can make specific antibodies and a T cell response to the flu vaccine. Even those with CVID can make an immune response and persons with XLA won’t produce antibodies - but will make a T cell response.

“We hope that may provide at least some immunity to change the severity of the COVID-19 infection,” said Dr. Ballow, adding that it could take nine months before reports are published in the literature about how effective vaccines are for persons with PI.

Dr. Ballow also addressed the question of the timing of immunoglobulin therapy and the vaccine. He said he is suggesting people may get their replacement Ig therapy about two weeks after the vaccine. Furthermore, concerning the question of when immunoglobulin will contain specific antibodies to the COVID-19 virus, Dr. Ballow said that wouldn’t happen until probably late 2021 or 2022.

Also, important to keep in mind is that even after receiving the vaccine, a person may still carry an asymptomatic viral infection, so continue to wash hands, wear a mask, and practice physical distancing.

Both Dr. Ballow and Dr. Walter reviewed recently released studies on how COVID-19 affects persons with PI. One study from Italy and another from New York City showed that those with PI who were older and had underlying comorbid conditions fared less well than those without these risk factors, similar to the general population.

“I think it’s a positive that, in general, persons with PI may not be at increased risk of mortality from COVID-19 unless they have underlying conditions that compromise their health like chronic lung disease, kidney disease, or a cancer like lymphoma,” said Dr. Ballow.

Similarly, Dr. Walter pointed to a Florida study that showed that in the pediatric population with allergic and immune disorders:

• Mostly young adults become infected and are symptomatic
• Asthma and obesity increases chances of hospitalization
• Maintenance of immunosuppressive medications decrease hospitalizations

Dr. Ballow suggested planning ahead by speaking to your doctor about COVID-19 specific monoclonal antibody treatments (made by Eli Lilly and Regeneron), should you test positive to COVID-19 or have exposure to someone close, for example a spouse that has tested positive to COVID-19. These monoclonal antibody treatments must be administered in a hospital infusion setting within ten days of the onset of symptoms after a positive viral COVID-19 test. The efficacy of the monoclonal antibody cocktails appears to be very high, he said.

Click here to listen to the presentation.