Vaccinating in the Time of COVID-19

Leading COVID-19 Vaccines

The type of vaccines making headlines these past few weeks are mRNA-based COVID-19 vaccine candidates. These vaccines use mRNA, which is genetic material that carries genetic code from a cell’s nucleus to the ribosomes and provides instructions on which proteins to build. In the case of the mRNA vaccines, the ribosomes start making spike proteins based on the viral mRNA in the vaccine. The body perceives these spike proteins as if the body has been infected and starts the process of creating antibodies and other defenses. [4]

“The development of vaccines to combat COVID-19 is critical for our psoriasis patients,” said Dr. April Armstrong, M.D., Professor of Dermatology at the University of Southern California and Chair of the Medical Board of the National Psoriasis Foundation (NPF). “We need to critically evaluate scientific data for these emerging vaccines and interpret these data with special consideration for our patients with psoriasis and psoriatic arthritis. Once available to our patients, we need to carefully monitor their effects in the real world.”

Both Pfizer, in partnership with BioNTech, and Moderna have announced efficacy data for their mRNA vaccine candidates and have filed for U.S. Emergency Use Authorizations. As of December 11, 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the Pfizer/BioNTech COVID-19 vaccine to be distributed in the U.S. [5] Distribution of the vaccine will be prioritized according to the populations identified by the CDC ACIP guidelines, with health care personnel and residents of long-term care facilities being offered the vaccine first. [6] Pfizer and BioNTech, in collaboration with other vaccine companies, are expected to supply hundreds of millions of vaccine doses to American citizens by the end of 2021. [7]

Following recommendations from the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC), the FDA has issued an EUA for the mRNA vaccine candidate from Pfizer and BioNTech SE, BNT162b2. [5][8][9] The New England Journal of Medicine published an article on the safety and efficacy of this vaccine, noting that a two-dose regimen of this vaccine was found to be safe and 95 percent effective against COVID-19, according to Phase 3 study data. Data from the study showed that the observed vaccine efficacy against COVID-19 reached full efficacy against the disease at least 7 days after the second dose. [10] Over 43,000 participants were involved in this Phase 3 study, with half receiving the vaccine and the other half receiving a placebo. There were 10 cases of COVID-19, however, 9 cases occurred in the placebo group and 1 in the vaccine group. The incidence of serious adverse events was low, with 4 related serious adverse events reported among vaccine recipients. These adverse effects include shoulder injury related to vaccination, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia. Overall, the safety profile for BNT162b2 was favorable, with reactogenicity being generally mild or moderate, and reactions less common and milder in older adults compared to younger adults. Systemic reactogenicity was more common and severe after the first dose, but local reactogenicity was found to be similar after both doses. Generally, reactogenicity events were short-lasting. [10]

Moderna’s mRNA-1273 vaccine candidate uses mRNA to encode for a prefusion stabilized form of the surface spike protein [11] Analysis of data from the Phase 3 clinical trial demonstrated a vaccine efficacy of 94.1 percent. While data from the Phase 3 study have not been published in a peer-reviewed publication yet, the company announced 30 severe cases of COVID-19 occurred during the Phase 3 trial, and all 30 cases occurred in the placebo group.11 The company also reported that the majority of adverse events were mild or moderate in severity and included: injection site redness/pain, fatigue, myalgia, arthralgia, headache, and pain. [12]

On December 17, the Center for Biologics Evaluation and Research’s (CBER) and VRBPAC will meet to discuss an EUA approval of the Moderna COVID-19 vaccine for the prevention of COVID-19.

“The first vaccines to be approved for COVID-19 will be mRNA-based. They make the body’s own cells produce pieces of the virus for a certain period of time so that the immune system can be ‘trained’ to see the virus without an actual infection. In this way, the immune system becomes better at clearing the virus when an exposure happens. mRNA vaccines are a new class; we do not know if they change the course of psoriatic disease. The AZD1222 vaccine uses a common cold virus that was modified to look more like the COVID-19 virus to train the immune system,” says Dr. Christoph Ellebrecht, M.D., department of dermatology at the University of Pennsylvania.

Another COVID-19 vaccine candidate is the AstraZeneca/Oxford vaccine (AZD1222), which uses a replication-deficient viral vector that is based on a weakened version of the adenovirus and contains the genetic material of SARS-CoV-2 spike protein. Once vaccinated, the surface spike protein is produced by the body, which primes the immune system to attack the SARs-CoV-2 virus if the person becomes infected later on. [13] Recent clinical trial data are demonstrated the vaccine meeting the primary endpoint of showing protection from COVID-19 occurring 14 days or more after patients received two doses of the vaccine. [13]

The Lancet has also published a peer-reviewed analysis of 4 clinical trials of AZD1222, evaluating its safety and efficacy. The analysis showed that the patients who received two standard doses experienced a vaccine efficacy of 62.1 percent and patients who received a low dose followed by the standard dose experienced an increased efficacy of 90 percent. Overall, efficacy across both groups was 70.4 percent. The vaccine also demonstrated an acceptable safety profile. Of the 11,636 clinical trial participants, 175 severe adverse events occurred in 168 participants: 84 events in the vaccine group and 91 in the control group. Of those events, only 3 were classified as possibly related to a vaccine. [14]

AstraZeneca is preparing to submit the data to regulatory authorities worldwide, seeking conditional or early approval. They are also seeking an Emergency Use Listing from the WHO. [13]

“While these clinical trial data are highly informative, it is equally important to evaluate their effectiveness and safety profile in the real world once they become available to most of our psoriasis community,” said Dr. Armstrong. “We need to exercise extreme caution when deciding whether to attribute an adverse event to the vaccine. Because untoward events can happen regardless of vaccination, we need to examine each case of adverse event following vaccination carefully, paying full attention to the ‘base rate’ of that event in the population before vaccination.”

Psoriatic Disease and Vaccination

Even though the focus has been on COVID-19 vaccination, staying up-to-date on all appropriate vaccinations can help maintain a patient’s overall health. Because of that, the NPF Medical Board is updating their guidance for vaccinating adult patients on systemic therapy for psoriasis, a project in which Dr. Ellebrecht is heavily involved. “This updated paper aims to use the heightened vaccine awareness to encourage providers and patients to engage in a conversation about their current vaccine status and give them up-to-date recommendations on what to do when you start or already are on systemic psoriatic disease treatment.”

As it stands now, vaccination in patients with psoriatic disease is generally recommended. However, it should be noted that live vaccines are contraindicated in patients on immunosuppressive therapy generally. [15] As infections are a major cause of morbidity and mortality in patients on chronic immunosuppression, vaccine status and advising should be discussed early in the management of patients with moderate-to-severe psoriasis. [15] NPF’s Medical Board reviewed the vaccines available at the time of writing and examined whether they should be recommended for patients on systemic therapies. According to that paper, certain vaccines should be given prior to starting systemic therapy, such as chickenpox, zoster, and specific pneumococcal vaccines. [15] 

 “Live vaccines should be given before starting systemic psoriasis treatment. Some therapies make vaccines less effective, which is why patients should talk to their provider about updating their vaccination status prior to starting such therapies,” says Dr. Ellebrecht. He continues, “ideally, age-appropriate vaccines should be given prior to starting systemic psoriatic disease therapy. Killed/inactivated vaccinations are generally safe while on treatment. They seem in most cases to still be effective in patients on treatment.”

Additionally, the NPF COVID-19 Task Force has updated their Guidance Statements to include the use of COVID-19 vaccines in patients with psoriatic disease. The new guidance statements in this update include:

• Patients with psoriatic disease, who do not have contraindications to vaccination, should receive a mRNA-based COVID-19 vaccine as soon as it becomes available to them based on federal, state, and local guidance. Systemic medications for psoriasis or psoriatic arthritis are not a contraindication to the mRNA-based COVID19 vaccine. If vaccine supply is limited, the Task Force recommends following CDC’s prioritization guidelines for early vaccination for selected groups based on their comorbidities and work setting.
• It is recommended that patients who are to receive a mRNA-based COVID-19 vaccine continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases. Shared decision-making between clinician and patient is recommended to guide discussions about use of systemic therapies during the pandemic.

Health care providers can read more about the NPF Covid-19 Task Force efforts and the guidance statements at the COVID-19 Resource Center.

References

[1] Vaccine Types. Vaccines. https://www.vaccines.gov/basics/types. Accessed December 13, 2020.

[1] Vaccine Types. National Institute of Allergy and Infectious Diseases. https://www.niaid.nih.gov/research/vaccine-types. Accessed December 13, 2020.

[1] Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington D.C. Public Health Foundation, 2015.

[1] Akpan N. Moderna's mRNA vaccine reaches its final phase. Here's how it works. National Geographic. https://www.nationalgeographic.com/science/2020/05/moderna-coronavirus-vaccine-how-it-works-cvd/. Published July 28, 2020. Accessed December 13, 2020.

[1] Pfizer-BioNTech COVID-19 Vaccine. U.S. Food and Drug Administration. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine. Published December 11, 2020. Accessed December 13, 2020.

[1] The Advisory Committee on Immunization Practices' Interim Recommendation for Allocating Initial Supplies of COVID-19 Vaccine - United States, 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/69/wr/mm6949e1.htm. Published December 10, 2020. Accessed December 13, 2020.

[1] Pfizer and BioNTech Celebrate Historic First Authorization in the U.S. of Vaccine to Prevent COVID-19. Pfizer. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-celebrate-historic-first-authorization. Published December 11, 2020. Accessed December 13, 2020.

[1] FDA Statement on Vaccines and Related Biological Products Advisory Committee Meeting. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-statement-vaccines-and-related-biological-products-advisory-committee-meeting. Published December 11, 2020. Accessed December 13, 2020.

[1] Pfizer and BioNTech Receive FDA Advisory Committee Vote Supporting Potential First Emergency Use Authorization for Vaccine to Combat COVID-19 in the U.S. Pfizer. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-receive-fda-advisory-committee-vote. Published December 10, 2020. Accessed December 13, 2020.

[1] Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine [published online ahead of print, 2020 Dec 10]. N Engl J Med. 2020;10.1056/NEJMoa2034577. doi:10.1056/NEJMoa2034577

[1] Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID-19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization. Moderna, Inc.