by Dr. C.H. Weaver M.D. updated 10/2022
The Pfizer-BioNTech COVID‐19, Moderna are available for active immunization to prevent COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In May, 2022 the FDA elected to limit the authorized use of the Janssen (JNJ) COVID-19 Vaccine due to an increased risk of thrombosis with thrombocytopenia syndrome (TTS).
There has now been 60 confirmed cases of TTS reported to the Vaccine Adverse Event Reporting System (VAERS) following the administration of the Janssen COVID-19 Vaccine; 9 of these cases resulted in death. The rate of TTS is 3.23 per million doses of vaccine administered. TTP symptoms begin approximately 1 to 2 weeks after vaccination and are more common in females 30 to 49 years old. Updated fact sheet for the Janssen COVID-19 Vaccine can be found here.50
The United States Food and Drug Administration amended the emergency use authorizations for the Moderna and the Pfizer-BioNTech Covid-19 vaccines to allow people with compromised immune systems unable to mount an adequate immune response against the virus to get a “booster” dose. The hope is that the booster dose will provide patients with improved protection similar to people without weakened immune systems. The amended EUAs apply only to third doses of the Pfizer and Moderna vaccines. New research in immunocompromised patients published shows that the Moderna vaccine increases antibody levels and research from Israel shows a booster dose reduces the risk of severe infection and hospitalization.34,36
Initially prioritized for essential workers, people over age 65 and individuals with underlying health conditions that increase the risk for severe COVID-19 vaccines are widely available throughout the United States to most individuals seeking vaccination and should be considered because vaccination prevents COVID-19 in cancer patients.
Fall 2022 Booster Update
The FDA has authorized bivalent COVID-19 booster vaccines from Moderna and Pfizer-BioNTech for emergency use in the United States for Fall 2022. The vaccines target both the original strain and omicron variant of SARS-CoV-2. The FDA said it will refer to the vaccines as “updated boosters.”
“The FDA has extensive experience with strain changes for annual influenza vaccines,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release. “The public can be assured that a great deal of care has been taken by the FDA to ensure that these bivalent COVID-19 vaccines meet our rigorous safety, effectiveness and manufacturing quality standards for emergency use authorization.”
Both messenger RNA vaccines combine the companies' original vaccines with another component targeting the omicron BA.4 and BA.5 subvariants, which the FDA noted are expected to circulate this fall.
Under the updated EUA, people aged 12 years or older are eligible to receive the Pfizer-BioNTech booster and adults aged 18 years or older are eligible for the Moderna booster, as long as it has been at least 2 months since they completed their primary series or received their most recent booster shot.
FDA Approves Moderna COVID-19 Vaccine Spikevax
A second COVID-19 vaccine has been granted full approval by the FDA. Spikevax, also known as the Moderna COVID-19 vaccine, was approved to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. The vaccine is administered intramuscularly as a series of 2 doses 1 month apart.
The approval was based on an ongoing randomized, placebo-controlled, observer-blind phase 3 trial showed Spikevax was 93% effective at preventing COVID-29 in individuals 18 years of age and older starting 14 days after the second dose. Among 14,287 vaccine recipients, there were 55 cases of COVID-19, while in the placebo group, which included 14,164 recipients, there were 744 cases.
The most common side effects were pain at the injection site, fatigue, headache, myalgia, chills, arthralgia, nausea/vomiting, axillary swelling/tenderness, fever, swelling at the injection site, and erythema at the injection site. The vaccine was also associated with an increased risk of myocarditis. The risk was observed to be highest among males 18 to 24 years old. Most of these cases resolved with conservative management, though some required intensive care support.48,49
FDA Authorizes Evusheld to Protect Immunocompromised Individuals
The United States Food and Drug Administration gave emergency use authorization (EUA) to Evusheld for use in preventing COVID in individuals with weakened immune systems who do not mount an effective immune response to vaccination. Evusheld is a long-acting monoclonal antibody developed by AstraZeneca that can stay active for months which should offer longer-lasting protection compared to the other currently monoclonal antibody treatments that are given to high-risk people already sick with Covid.
Thousands of individuals with compromised immune systems are at increased risk from COVID because they are unable to mount an effective immune response to vaccination against SARS-CoV2. Those are greatest risk are individuals with blood cancers, those on immunosuppressive cancer therapy, transplant recipients and individuals with other immune mediated disorders.
Evusheld is a combination of two long-acting monoclonal antibodies directed against the SARS-CoV-2 virus and is the first and only antibody therapy authorized in the US for COVID-19 pre-exposure prophylaxis. Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. Tixagevimab and cilgavimab are long-acting monoclonal antibodies that are specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment and entry into human cells. Tixagevimab and cilgavimab bind to different, non-overlapping sites on the spike protein of the virus.
Evusheld is given via an intramuscular injection and has been shown to be strongly effective at preventing COVID in a clinical trial, reducing the risk of developing a symptomatic infection by 83%. The F.D.A. approval is for individuals with blood cancer, transplant recipients and people taking drugs that suppress their immune system.
The primary data supporting this EUA for Evusheld are from the PROVENT clinical trial in adults greater than age 59 or with a prespecified chronic medical condition or at increased risk of SARS-CoV-2 infection for other reasons who had not received a COVID-19 vaccine and did not have a history of SARS-CoV-2 infection or test positive for SARS-CoV-2 infection at the start of the trial. The main outcome measured in the trial was whether a trial participant had a first case of COVID-19 after receiving Evusheld . In the trial 3,441 people received Evusheld and 1,731 received a placebo. Evusheld recipients saw a 77% reduced risk of developing COVID-19 compared to those who received a placebo. In additional analyses, the reduction in risk of developing COVID-19 was maintained for Evusheld recipients through six months.
Additional data from an independent study conducted by investigators at the Food and Drug Administration show that the long-acting antibody therapy Evusheld (tixagevimab co-packaged with cilgavimab) retains neutralizing activity against the SARS-CoV-2 Omicron variant (B.1.1.529).45
Results from 2 confirmatory tests show that the neutralizing potency of the antibody combination was within the range of neutralizing titers found in an individual previously infected with COVID-19. Results from the phase 3 TACKLE trial showed that treatment with Evusheld reduced the risk of developing severe COVID-19 or death from any cause by 50% compared with placebo in non-hospitalized patients with mild to moderate COVID-19 who were symptomatic for 7 days or less.45
Possible side effects of Evusheld include hypersensitivity reactions (including anaphylaxis), bleeding at the injection site, headache, fatigue and cough. The safety and effectiveness of Evusheld for use in the pre-exposure prevention of COVID-19 will continue to be evaluated.39
Data on Vaccine Effectiveness
The VOICE study measured responses to Moderna’s two-dose mRNA-1273 vaccine. The study enrolled 791 patients with solid tumors from hospitals throughout the Netherlands and placed them in four cohorts: individuals without cancer; patients with cancer treated with immunotherapy; patients treated with chemotherapy; and patients treated with a chemo-immunotherapy combination. The patients received antibody tests 28 days after the second shot. Adequate antibody levels – by the researchers’ own definition – were found in 84% of patients receiving chemotherapy, 93% receiving immunotherapy, and 89% receiving a chemo-immunotherapy combination, compared to 99.6% of individuals without cancer.38
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Preliminary laboratory data suggest that 2 doses of the Pfizer-BioNTech COVID-19 vaccine may not be sufficient to protect against infection with the SARS-CoV-2 Omicron (B.1.1.529) variant. Findings demonstrated a 25-fold increase in neutralizing antibody titers in individuals who received the third dose, providing a similar level of neutralization against Omicron as was observed after 2 doses against the wild-type strain. “Although 2 doses of the vaccine may still offer protection against severe disease caused by the Omicron strain, it’s clear from these preliminary data that protection is improved with a third dose of our vaccine,” said Albert Bourla, Chairman and CEO, Pfizer. A third dose of the vaccine also increased CD8+ T cell levels against multiple spike protein epitopes, correlating with protection against severe disease. An Omicron-specific COVID-19 vaccine is currently being developed in the event that it is needed and may be available by March 2022. Data from previous clinical trials evaluating variant specific vaccines will also be submitted to regulatory agencies in order to speed up the process of adapting the vaccine and gaining authorization or approval.40
ReferencePfizer and BioNTech provide update on Omicron variant.40
Effective in Cancer Patients
The relative risk of developing COVID-19 was more than 20 times higher for unvaccinated patients with cancer than for vaccinated patients with cancer, according to findings from a real-world study in over 1000 patients presented at the European Society for Medical Oncology Congress 2021. The relative risk of developing COVID-19 was 21.5 times higher among unvaccinated patients than among vaccinated patients. Most vaccinated patients reported no side effects (39%) or mild ones (43%) and 2.4% reported severe side effects typically lasted 1 to 3 days. The most common were sore arm, headache, fatigue, and increased temperature. Less common were swollen lymph nodes (0.7%) and allergic reactions (0.7%).35
Safety in Cancer Patients
Research published in February 2022 confirms that mRNA vaccines are just as safe for people with cancer as they are for cancer-free individuals. Researchers from Fox Chase Cancer Center tracked short-term side-effects from more than 1,753 recipients of the Pfizer BNT162b2 vaccine, and found no additional reactions for patients undergoing active cancer treatment (surgery, chemotherapy, immunotherapy, or radiation therapy) or who had completed treatment.
The results come from in person, phone and online surveys given to people who received two doses of the mRNA vaccine, three weeks apart, between February 16 and May 15, 2021. 1,183 people with a history of cancer responded to both surveys, with 17.8% then currently undergoing treatment. Respondents experienced pain at the injection site, muscle pain, joint pain, fever, chills, headache, nausea, and fatigue at similar rates as those reported by people without cancer from the original clinical trials. Adverse effects for people undergoing immunotherapy also mirrored those in the general population.46
The two-dose Pfizer-BioNTech COVID-19 vaccine provides an effective immune response and is safe in people undergoing treatment for certain types of cancer, according to a study published in the June 2021, JAMA Oncology. Compared to individuals without cancer however, people with breast, colon and lung cancers, appear to have a "lagging" immune response to the vaccine.
Israeli researchers compared antibody responses after vaccination with the Pfizer-BioNTech vaccine in 232 adults receiving chemotherapy or radiation treatment for cancer with those of 220 healthy adults. After the first dose, 29% of the cancer patients had detectable antibodies in their blood, compared with 84% of those without the disease and 86% had detectable levels in their blood after the second dose. The researchers, who are monitoring the cancer patients for six months to determine if their immune response declines and a booster dose is needed.
Additional Dose and Booster Shot
Pfizer-BioNTech COVID-19 vaccine administration of a “booster” vaccine 6 months after the primary 2-dose series elicits high neutralization titers against both the wild type and the Beta variant (B.1.351) Corona Virus. A third dose further boosts antibody titers against the Delta variant, and new research shows that the booster reduces the risk of severe illness and hospitalization from.36
Moderna: Moderna reports its vaccine is 93% effective six months after the second dose. It’s important to understand however that immunity against the coronavirus will continue to wane and eventually diminish vaccine efficacy. To improve vaccine effectiveness Moderna also believes a booster shoot will likely be necessary prior to the winter season. Study results suggest a booster dose produced a “robust” antibody response against three variants, including delta. Israel has already announced the country would give booster doses to its elderly population.33
Vaccine effectiveness diminishes over time, and a booster "is needed within six to 12 months after full vaccination.28,29 Data from Israel published Sept 15, 2021 shows that a booster reduces the risk of severe infection and hospitalization.36 A study of COVID vaccine boosters suggests Moderna or Pfizer works best and both were approved by the FDA in October 2021 - reversing the previous position.
A study by the National Institutes of Health suggested people who got the J&J vaccine as their initial vaccination against the coronavirus may get their best protection from choosing an mRNA vaccine as the booster. If you got the Johnson & Johnson vaccine as your first COVID-19 shot, a booster dose of either the Moderna or Pfizer-BioNTech vaccine apparently could produce a stronger immune response than a second dose of J&J's vaccine. And if you started out with either Pfizer or Moderna, it probably doesn't matter that much.
The bodies adaptive immune system targets specific viruses by producing antibodies against a unique virus like COVID-19 to protect us in both the short and long term. When the bodies B and T lymphocyte cells respond to a virus they create germinal centers in the lymph nodes which is where plasma cells learn how to make antibodies to fight the COVID-19 infection. The germinal centers also produce memory cells which go into action and eliminate an infection when your re-exposed. Recent research suggests germinal centers take 15 weeks or longer to form after vaccination and their production of memory cells may provide longer term immunity to COVID-19 lasting years.30 Studies have shown however that the levels of neutralizing antibodies generated by the COVID vaccines do decline over time.31
Israel’s Ministry of Health has reported a decrease in vaccine effectiveness over time to 64% for preventing both infection and symptomatic illness but remains 93% effective in preventing serious illness and hospitalization.32 Although the vaccine may no longer be producing levels of antibodies that protect people entirely from infection, the long-term memory response is still working and protecting people from serious illness and death.
Pfizer said that a third dose of its vaccine elicits an antibody response five to 10 times higher than after two doses. Measuring antibody levels as a surrogate endpoint for effectiveness to guide policy however may be the wrong measure – what we really care about is preventing serious illness. The U.K. government in fact recently announced that they are considering using actual serious COVID illness as a benchmark for guiding policy instead of infection as measured by antibodies.
Currently non-immunocompromised fully vaccinated individuals appear to have the best available protection against serious illness from COVID-19 and focusing on getting the unvaccinated vaccinated should remain a priority. But what’s the harm in being prepared for the time when boosters may be needed? Developing a booster and getting safety data should be a priority especially for those most at risk. Our responsibility should be to protect those who are most vulnerable.