COVID-19 Vaccine Education Nursing CE Course

onding individually to each pathogen it encounters. The adaptive immune system is activated if an invading pathogen somehow breaches innate immune mechanisms. Due to adaptation, the acquired immune system responds comparatively slower than the innate immune system. The adaptive immune system boasts immunologic memory and specificity, meaning it “remembers” prior antigens and can develop a repeat specified response. There are three types of adaptive immunity: humoral immunity, cell-mediated immunity, and T-regulatory cells. The immune system organs are positioned strategically throughout the body. They are referred to as lymphoid organs because they house macrophages and lymphocytes, the two key mediators of the adaptive immune system. Macrophages engulf and digest germs and dead cells, leaving behind antigens for the body to identify as dangerous, triggering the stimulation of antibodies. There are two main types of lymphocytes: B-Lymphocytes (B-cells) and T-lymphocytes (T-cells). B-cells mediate the production of antibodies that attack antigens left behind by the macrophages. B-cells bind directly with unique proteins on the invading antigen's surface and then hand the baton to the T-cells, who have the job of attacking the target cells. T-cells attack cells in the body that have already been infected. They lyse the infected cells, provide immunity against most pathogens, and aid in antibody production. Humoral immunity is mediated by B-cells and results in the production of immunoglobulins (Ig), otherwise known as antibodies. T-cells and their cytokine products facilitate cell-mediated immunity, which does not involve antibodies. Instead, cell-mediated immunity includes cytotoxic T-cells (usually CD8) and helper T-cells (usually CD4).  T-regulatory cells, also known as suppressor T-cells, display the markers CD4 and CD25 and limit other immune effector cells’ activity. Ultimately, their primary role is to prevent damage to normal tissues and lessen the inflammatory response. Vaccination is an example of acquired immunity (Longo, 2019; McCance & Heuther, 2019).

Vaccination

To end the COVID-19 pandemic, a large proportion of the world needs to develop immunity to the virus. The safest and most effective way to accomplish this is through vaccination. Vaccines work by impersonating the infectious bacteria or viruses that inflict disease to prompt the body to create antibodies that fight the condition upon exposure. Vaccination is a prime example of adaptive immunity, as it prompts the creation of antibodies against a pathogen to prevent the acquisition of the illness later. If that particular pathogen tries to invade the body, the adaptive immune system responds more quickly, producing additional antibodies to address the infection and thwart illness. Vaccination stimulates the body’s immune system to build up defenses against the infectious organism without inducing the disease. The most common types of vaccines contain a weakened version or inactivated parts of a particular organism to trigger an immune response. Typically, the vaccine is comprised of a minuscule, weakened, and a non-dangerous fragment of the organism that includes specific parts of the antigen. This tiny amount is enough for the body to learn how to build the specific antibody in the event of an encounter with the real antigen later. More novel vaccines contain the blueprint for producing antigens rather than the antigen itself. Regardless of whether the vaccine is made up of the antigen itself or the blueprint so that the body will produce the antigen, the recipient does not acquire the illness from the vaccine. Some vaccines require multiple doses, given weeks or months apart. This is sometimes needed to allow for the production of long-lived antibodies and the development of long-standing memory cells. Table 1 provides a comparison of the major types of vaccines used throughout the US (Centers for Disease Control and Prevention [CDC], 2018; McCance & Heuther, 2019; WHO, 2020).

Vaccine Development and FDA Regulation

Vaccine development is traditionally a prolonged, multi-step, and intricate process that takes at least 10 years of research and testing before the vaccine is brought to market. The FDA is the regulatory authority that oversees the safety, effectiveness, and quality of vaccines before approving them for use in the US. The year 2020 has been marked by significant uncertainty, turmoil, and tragedy brought forth by the COVID-19 virus; but is also characterized by the fastest vaccine developed in the US to date. An emergency use authorization (EUA) is issued by the US Food & Drug Administration (FDA) to allow access to critical medications and medical products that may help during a public health emergency. An EUA is different from standard medical testing, medication, or vaccination approval and must meet the following criteria (FDA, 2020, 2021a):

• The product will be used for a serious or life-threatening disease or condition.
• Based on the totality of scientific evidence available, it is reasonable to believe the product may be effective.
• The known and potential benefits of the product outweigh the known and potential risks of the product.
• There are no adequate FDA-approved alternatives available.

Once a COVID-19 vaccine receives an EUA, the FDA mandates ongoing safety monitoring and reporting. Healthcare providers must adhere to the following conditions of an EUA:

• providing the recipient/caregiver the Fact Sheet for Recipients (similar to a vaccine information statement [VIS] for licensed vaccines), which communicates vaccine benefits and risks to the recipient via hard copy or electronic means
• reporting vaccine administration data to CDC
• reporting vaccine administration errors and specified adverse events to Vaccine Adverse Effect Reporting System (VAERS), a nationwide online system led by the US Department of Health and Human Services (HHS) that collects reports of adverse events following vaccination (CDC, 2020b; HHS, n.d.).

As an added measure of data collection, the FDA has also developed v-safe, a novel, voluntary, smartphone-based application tool that uses text messaging and internet-based surveys to facilitate the collection of additional COVID-19 vaccination-related side effects. This tool generates automated daily check-ins for COVID-19 vaccine recipients, allowing them to directly report any side effects in real-time. It allows for the estimation of rates of local and systemic reactions and clinically important adverse effects following vaccination. V-safe also provides recipients with reminders on obtaining their second COVID-19 vaccine dose (CDC, 2020b; HHS, n.d.).

COVID-19 Vaccines

In early February, 2021, two very similar vaccines were approved for EUA in the US; Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273). A third vaccine by Johnson & Johnson/JNJ-78436735 (Ad26.COV2.S) received FDA approval on February 27, 2021. Researchers worldwide are testing more than 65 vaccines in clinical trials on humans, and 20 have reached the final stages of testing. Several other vaccines are approved for early emergency use in other countries, such as Gamaleya (Sputnik V) in Russia and Astrazeneca ChAdOx1 nCoV-19 (AZD1222) in India. Before delving into the details of the COVID-19 vaccines available in the US, the next section dispels some of the most common COVID-19 vaccine misconceptions (CDC, 2020a, 2020b; FDA, 2021b; Vizient, 2021; Zimmer et al., 2021). 

Vaccine Myths and Realities (CDC, 2020b; Sax, 2021)

• Myth: COVID-19 vaccines were ‘rushed,’ so they should not be trusted.
• Reality: You cannot rush safety trials; researchers and drug manufacturers were allowed to focus solely on this one task, and the government removed several of the bureaucratic inefficiencies that most commonly slow down the process.
• Myth: You can get a COVID-19 infection from the vaccine.
• Reality: The vaccine cannot cause an infection with the SARS-COV-2 virus because it is not an inactivated (attenuated) version of the virus.
• Myth: The vaccine can change your DNA.
• Reality: The vaccine can't change, interact with, or affect human DNA (i.e., genetic material) since it is a messenger ribonucleic acid (mRNA) vaccine that never enters the nucleus of the cells where the DNA is stored.
• Myth: The vaccine can cause genetic changes in pregnant women and women of childbearing age, leading to fetal harm and infertility.
• Reality: Since the COVID-19 vaccines do not enter the nucleus and do not alter human DNA, they cannot cause genetic changes in the woman, fetus, infant or impact future pregnancies. 
• Myth: Once you’ve been vaccinated, you cannot spread the virus and no longer need to wear a mask or practice social distancing.
• Reality: It is not clear if vaccine recipients are capable of spreading the virus to others. As of February 2021, data only demonstrates that the vaccine effectively prevents serious symptoms in the vaccine recipient. It remains crucial that vaccine recipients continue to follow all of the CDC guidelines to prevent the spread of COVID-19, including wearing masks, handwashing, and social distancing. 
• Myth: You don’t need to be vaccinated if you had a prior COVID-19 infection.
• Reality: The duration and effectiveness of natural immunity after a COVID-19 infection is unclear and varies between individuals but has shown to be decline over time. Research demonstrates that the COVID-19 vaccines are skilled at prompting a significant immune response to the target protein responsible for preventing the infection, thereby enhancing a directed immune response. Therefore, the CDC recommends that anyone who had a prior COVID-19 infection should be vaccinated following a 90-day symptom-free period.

Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) mRNA Vaccines

Disclaimer: For the remainder of this module, the Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 vaccines will be referred to as ‘Pfizer’ and ‘Moderna,’ respectively. 

Pfizer and Moderna not only developed the first two COVID-19 vaccines in the US, but their agents are very similar with regards to their chemical structure, technology, and mechanism of building immunity. Both vaccines use novel messenger RNA (mRNA) to generate immunity to COVID-19, which has been studied and broadly tested by scientists for more than a decade but has never before been brought to market. Immunity generated from mRNA vaccines is distinct from traditional vaccines as they do not contain a weakened or inactivated version of the COVID-19 virus; thus, there is no potential risk of infection or insertional mutagenesis. These vaccines contain only the genetic material for a specific protein, and no genetic material enters the nucleus of the cells. When the vaccine is injected, the mRNA is taken up by macrophages near the injection site.  The mRNA provides a blueprint (i.e., instructions) to the immune system cells, teaching them how to create the S protein unique to SARS-CoV-2. The S protein subsequently appears on the macrophages' surface, triggering the body’s immune response and directing the production of antibodies that recognize and react to the S protein. Once the mRNA has completed its task, it is rapidly degraded by enzymes and removed from the body. This enzymatic degradation process occurs naturally in the body to remove dead, unwanted, or damaged cells (CDC, 2020b; Sax, 2021).

Both the Pfizer and Moderna vaccines have shown impressive and near equivalent efficacy across clinical trials. The Pfizer vaccine demonstrated nearly 95% efficacy at preventing symptomatic COVID-19 infection about 10 days following receipt of the second dose. Data demonstrated that the vaccine appeared to be relatively equally effective across demographic groups (i.e., age, racial and ethnic groups). The Moderna vaccine was about 94% effective in preventing symptomatic COVID-19 infection at 10 to 14 days following the second dose. Efficacy appeared to be marginally lower in individuals aged 65 and older; however, the numbers could have been influenced by the fact that there were fewer cases in that age group during the clinical trial. High efficacy (≥ 86%) was observed across age, sex, race, and ethnicity categories and persons with underlying medical conditions. Both vaccines require a two-dose series, and the specifics regarding dosing and administration schedules are outlined in Table 2 (CDC, 2020a, 2020b, 2021; Vizient, 2021).

According to the CDC (2021), second doses administered up to 4 days earlier than recommended are considered valid (i.e., Moderna may be administered on days 24 to 27; Pfizer may be administered on days 17 to 20). However, efforts should be made to administer the second dose as close to the recommended interval as possible. If adhering to the recommended timelines is not feasible, the second dose may be scheduled for administration up to 6 weeks (42 days) after the first dose. Further, both doses are necessary for protection as the efficacy of a single dose has not been formally studied in clinical trials (CDC, 2021). As of February 2021, there are few absolute contraindications to mRNA vaccines, which include the following:

• severe allergic reaction (e.g., anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components,
• an immediate allergic reaction of any severity to a prior dose of an mRNA COVID-19 vaccine or any of its components (including polyethylene glycol [PEG], or polysorbate)
  • PEG is an ingredient in both mRNA COVID-19 vaccines structurally related to polysorbate, and cross-reactive hypersensitivity between the compounds may occur (CDC, 2021; Vizient, 2021).

The CDC (2021) defines an immediate allergic reaction as any HSR or symptoms consistent with urticaria, angioedema, respiratory distress (e.g., wheezing, stridor), or anaphylaxis that occurs within 4 hours of administration. Patients meeting any of the above criteria should not be vaccinated with the second dose and should instead be referred to an allergist/immunologist (CDC, 2021; Vizient, 2021). Anaphylactic reactions in persons receiving mRNA COVID-19 vaccines outside of clinical trials have been reported. The CDC (2020a) recommends that healthcare professionals become familiar with identifying immediate-type allergic reactions and have a plan in place to respond to these emergencies. The following medications and equipment should be readily available at all sites where mRNA vaccines are administered:

• at least three prefilled syringes of epinephrine or autoinjectors
• antihistamines 
  • histamine-1 (H1) blocker, such as diphenhydramine (Benadryl)
  • histamine-2 (H2) blocker, such as famotidine (Pepcid)
  • antihistamines may be given as adjunctive therapy but should not be used as the initial or sole treatment for suspected anaphylaxis 
• pulse oximeter
• supplemental O2 
• bronchodilators (e.g., albuterol [ProAir])
• IV fluids
• intubation kit (CDC, 2020a, 2021)

Table 3 compares the side effect profiles of the Pfizer and Moderna vaccines.

Receipt of either the Pfizer or Moderna vaccine will not affect the results of RT-PCR or antigen COVID-19 tests performed after vaccination. These tests are used to detect active disease and not immunity, and the vaccine does not cause the virus or induce viral replication. Therefore, if a patient who has previously received the vaccine subsequently has a positive RT-PCR or other antigen test, they should be treated as an active COVID-19 infection. Since the vaccine is intended to induce an immune response, an antibody test may be positive in someone who has been vaccinated. However, the time from vaccine administration to measurable levels of antibodies has not yet been determined. Information regarding the durability of protection following receipt of either mRNA vaccine is not yet available. Data from the Moderna trial suggests that antibodies were highest for about 4 months, with titers slightly declining over time. Since there is no information on how long the vaccines will be protective as of February 2021, there is no recommendation for booster doses following completion of the two-dose vaccination series (CDC, 2020a; Sax, 2021).

Clinical Considerations for mRNA Vaccine Use in Special Populations

Prior History of COVID-19 Infection

Data from clinical trials indicate that mRNA COVID-19 vaccines can safely be given to persons with evidence of a prior COVID-19 infection. Vaccination should be offered to persons regardless of a history of a prior symptomatic or asymptomatic COVID-19 infection. Viral RT-PCR or antigen testing for an acute COVID-19 infection or serologic testing to assess a prior infection is not recommended before vaccination (CDC, 2020a, 2021).

Current COVID-19 Infection

Vaccination of individuals with known current COVID-19 infection should be deferred until the person has recovered from the acute illness (resolution of symptoms) and criteria have been met to discontinue the isolation period. This recommendation applies to persons who develop a COVID-19 infection before receiving any vaccine doses and those who develop an acute infection after their first dose but before receipt of the second dose. There is no recommended minimum time interval between infection and vaccination. As of February 2021, evidence suggests that the risk of COVID-19 reinfection is lowest in the first 3 months (90 days) after initial infection but may increase with time due to waning immunity. Thus, while vaccine supply remains limited, persons with recent documented COVID-19 infection may choose to temporarily delay vaccination, if desired, during this 90-day period. However, these individuals should be informed of the risk of reinfection with waning immunity and the continued need to complete the vaccination series despite prior COVID-19 infection. For vaccinated persons who subsequently develop a COVID-19 infection, prior receipt of an mRNA COVID-19 vaccine should not affect treatment decisions or the timing of treatments (including the use of monoclonal antibodies, convalescent plasma, antiviral therapy, or corticosteroid administration; CDC, 2020a, 2021; NIH, 2021; Vizient, 2021).

Post-exposure Prophylaxis

It is important to note that mRNA vaccines are not recommended for outbreak management or post-exposure prophylaxis. In other words, the mRNA vaccines are not indicated nor considered effective in preventing the development of infection in a person with a known exposure in the days before vaccination. It is deemed unlikely that the first dose of an mRNA COVID-19 vaccine would provide an adequate immune response within the incubation period to allow for effective post-exposure prophylaxis and therefore is not recommended at this time (CDC, 2020a, 2021).

Persons who Previously Received Passive Antibody Therapy

As of February 2021, there are no data on the safety and efficacy of mRNA COVID-19 vaccines in persons who received monoclonal antibodies or convalescent plasma as part of COVID-19 treatment. Based on the estimated half-life of such therapies as well as evidence suggesting that reinfection is uncommon in the 90 days after initial infection, vaccination should be deferred for at least 90 days as a precautionary measure until additional information becomes available to avoid the potential interference of the antibody therapy with vaccine-induced immune responses. This recommendation applies to persons who receive passive antibody therapy before receiving any vaccine doses, as well as those who receive passive antibody therapy after the first dose but before the second dose, in which case the second dose should be deferred for at least 90 days following receipt of the antibody therapy. For persons receiving antibody therapies for indications not related to COVID-19 (i.e., for autoimmune conditions or cancer therapy), the administration of mRNA COVID-19 vaccines either simultaneously with or at any interval before or after receipt of an antibody-containing product is considered unlikely to substantially impair the development of a protective antibody response. Therefore, there is no recommended minimum interval between non-COVID-19-related antibody therapies and receipt of one of the mRNA COVID-19 vaccines (CDC, 2020a, 2021)

Pregnancy and Lactation

Pregnancy alone (apart from occupational-related risk for those in healthcare or other front-line workers) places women in a high-priority group and thereby eligible for vaccination. Pregnancy has been identified as a condition that increases the risk of serious illness with a COVID-19 infection, including hospitalization, ventilation requirement, and death. The American College of Obstetricians and Gynecologists (ACOG, 2021) and the CDC (2020a) collectively support and recommend vaccination in women of reproductive age during pregnancy and lactation based on the established priority criteria. ACOG (2021) last updated their statement on February 4, 2021, and summary of their major recommendations are as follows:

• Since the mRNA vaccines are not live virus vaccines and they do not enter the nucleus or alter human DNA, they cannot cause any genetic changes in the woman, fetus, infant or impact future pregnancies.
• Pregnancy testing should not be a requirement before receiving one of these mRNA COVID-19 vaccines.
• It is not necessary to delay pregnancy until after completing both doses of these mRNA COVID-19 vaccines.
• If a woman learns that she is pregnant after the first dose of the vaccine, she should still complete the series and receive her second dose on schedule. 
• ACOG recommends that mRNA COVID-19 vaccines not be withheld from pregnant individuals who meet the vaccination criteria based on the CDC's recommended priority groups.
• COVID-19 vaccines should be offered to lactating individuals similar to non-lactating individuals when they meet the criteria for receiving the vaccine based on the CDC's prioritization groups.

Cancer and Other Immunocompromised Conditions 

COVID-19 continues to place a significant burden on health systems across the world. Patients with cancer have increased susceptibility to COVID-19 and face reduced access to care due to competition and finite resources. The preliminary recommendations from the National Comprehensive Cancer Network (NCCN, 2021) COVID-19 Vaccination Advisory Committee were released on January 22, 2021. Large cohort studies have demonstrated that cancer patients are at high-risk for COVID-19 infection and associated complications. There is a clear need for vaccinating cancer patients to avoid excess morbidity and mortality in this at-risk population. Therefore, the NCCN (2021) advises that individuals with active cancer or with active, recent (less than 6 months), or planned cancer treatment should be considered among the highest priority groups to receive COVID-19 vaccination. The NCCN (2021) recommendations include the following:

• Cancer patients must be appropriately educated that although these vaccines have shown to be safe and effective in the general population, their safety profile and effectiveness among cancer patients is unknown.
• Patients with active cancer on treatment, those planned to start treatment, and those less than 6 months posttreatment should be prioritized for vaccination and should be immunized when vaccination is available to them
  • this does not apply to those receiving only hormonal therapies
  • immunization is recommended for these groups, with the understanding that there are limited safety and efficacy data in these patients 
• Reasons to delay vaccination in this population are similar to those outlined for the general public (i.e., recent infection with COVID-19), and cancer-specific factors (i.e., those receiving intensive cytotoxic chemotherapy should delay until recovery of the absolute neutrophil count [ANC] as per the discretion of the treating clinician).
• Vaccination should be delayed for at least 3 months following hematopoietic cell transplantation or engineered cellular therapy (i.e., chimeric antigen receptor T-cell therapy [CAR-T]) to maximize the efficacy of the vaccine.
• Caregivers and household/close contacts of persons meeting the above criteria should be immunized when possible.

Persons with other immunocompromising conditions such as HIV and those prescribed non-cancer immunosuppressive agents might be at increased risk for severe COVID-19 infection. The CDC (2021) recommends that these persons are vaccinated with no contraindications. However, these individuals must be appropriately counseled on the unknown vaccine safety and efficacy profiles in immunocompromised persons and the potential for a reduced immune response to the vaccine (CDC, 2021). 

JNJ-78436735 (Ad26.COV2.S) Vaccine

Janssen Pharmaceuticals is a Belgium-based division of Johnson & Johnson that has been instrumental in developing the JNJ-78436735 (Ad26.COV2.S) vaccination. As noted above, the vaccination received EUA from the FDA on February 27, 2021 and has already begun distribution throughout the US. They expect to supply 100 million doses to the US by mid-2021. The JNJ-78436735 (Ad26.COV2.S) vaccine is based on the virus’s genetic instructions for building the S protein; however, it is distinct from the Pfizer-BioNTech and Moderna mRNA vaccines since it uses double-stranded DNA (instead of single-stranded RNA) to store the instructions. With this vaccine, a gene for the coronavirus S protein was added to another virus called adenovirus 26. Adenoviruses are a group of common viruses that cause cold or flu-like symptoms. Utilizing recombinant, replication-defective adenovirus type 26 vector leveraging technology, the company modified a version of the human adenovirus. Due to genetic alterations, the adenovirus vector can enter cells but cannot replicate once inside them or cause illness. Once the double-stranded DNA is injected, the host cells generate the S protein, stimulating the body’s immune response to produce unique antibodies. The JNJ-78436735 (Ad26.COV2.S) only requires a single dose, not a two-dose series. The vaccine was studied in the Phase 3 ENSEMBLE study, a randomized, double-blind, placebo-controlled clinical trial in adults 18 years old and older. The trial was conducted in eight countries and enrolled more than 45,000 individuals. It included a diverse and broad population, with significant representation of Black, Hispanic/Latin, Native American, and Alaskan Native participants. The study enrolled 44% of participants in the US, 55% male, and 41% of participants had comorbidities associated with an increased risk for progression to severe COVID-19, including obesity (28.5%), type 2 diabetes (7.3%), hypertension (10.3%), and HIV (2.8%) (US National Library of Medicine, 2021). According to a press release, the Phase 3 ENSEMBLE clinical trial demonstrated that the investigational single-dose vaccine met all primary and secondary endpoints, assessed at day 14 and 28-time points. The company released the following findings regarding the efficacy of the JNJ-78436735 (Ad26.COV2.S) vaccine:

• 72% effective in the US 
• 66% effective overall in preventing moderate to severe COVID-19, 28 days after administration 
• 85% effective overall in preventing severe disease and demonstrated complete protection against COVID-19 related hospitalization and death as of day 28
• protection against severe disease across multiple virus variants, including the SARS-CoV-2 Variant from the B.1.351 lineage observed in South Africa (Johnson & Johnson, 2021a, 2021b).

The most frequent overall adverse effects cited in phase 1/2 trials include fatigue, headache, myalgia, and injection-site pain. Most events were grade 1 or 2 in severity, and systemic effects were more common in those aged 55 and younger than adults aged 65 and older. Information regarding its safety and efficacy in special populations, such as pregnant women and immunocompromised patients, is not yet available (Johnson & Johnson, 2021a, 2021b; Vizient, 2021).

ChAdOx1 nCoV-19 (AZD1222) Vaccine (Oxford-Astrazeneca)

The ChAdOx1 nCoV-19 (AZD1222) COVID-19 vaccine is a product of the University of Oxford and AstraZeneca’s combined efforts. While not yet approved for use in the US, it has received an EUA in Britain since December 2020 and other parts of Europe. On January 3, 2021, India authorized the use of a version of this vaccine called Covisheild. The ChAdOx1 nCoV-19 (AZD1222) vaccine is very similar to the JNJ-78436735 (Ad26.COV2.S) vaccine. It is a replication-defective vectored vaccine using an adenovirus vector. Researchers initially genetically engineered an adenovirus that typically infects monkeys, and they found that it protected animals from COVID-19 infections by raising antibodies and other immune defenses against the virus. Phase 2/3 trials were initially launched in the UK and India, followed by additional trials in Brazil, South Africa, and the US. The pharmacology and mechanism of mounting immunity are identical to the JNJ-78436735 (Ad26.COV2.S) vaccine described earlier. However, it is a two-dose vaccination series with the second dose administered between 4 and 12 weeks following the first. In phase 2/3 UK trials, the most common side effects included pain and tenderness at the injection site, fatigue, headache, fevers, and myalgias (ASHP, 2021; Voysey et al., 2021a, 2021b). 

In November 2020, they announced that the vaccine had promising efficacy based on a study of the first 131 cases of COVID-19 trials in the UK and Brazil. However, while all volunteers received both doses, the first dose was only half-strength in some cases. Their findings demonstrated surprising results, as an initial half-strength dose led to 90% efficacy, while the two standard-dose shots led only to 62% efficacy. The lower dose resulted from a mistake in how the vaccines were measured and were not part of the original trial plan. Further, the half-strength was only administered to volunteers under 55 years, thereby obstructing the data's accurate extrapolation. Accounting for the mistake, the strength of the preliminary results was indeterminate. Recently, AstraZeneca released a statement announcing that the two doses (separated by 12 weeks) had an efficacy rate of 82.4%. On February 1, 2021, data from the phase 3 efficacy trials were released in a preprint with the Lancet, describing the safety of the two-dose vaccination series and the durability of the antibody levels by day 90. Further, efficacy was higher among those who received the second dose at 12 weeks than 6 weeks. Additionally, they reported that the vaccine protected people from getting sick and reduced the transmission of COVID-19 (Voysey et al., 2021a, 2021b). South Africa had planned to distribute 1 million doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine but announced their decision to halt these plans on February 7, 2021. A small trial failed to demonstrate that the vaccine protected against an emerging variant of COVID-19 (B.1.351), widespread in the area (American Association for the Advancement of Science, 2021). Many questions remain unanswered regarding the ChAdOx1 nCoV-19 (AZD1222) vaccine, its side effects, the durability of antibodies, and its use in special populations (The New York Times, 2021; Zimmer et al., 2021).

NVX-CoV2373 (Novavax) Vaccine

The NVX-CoV2373 (Novavax) is a recombinant nanoparticle vaccine created by Novavax, a small, Maryland-based pharmaceutical company. NVX-CoV2373 is a protein-based subunit vaccine that works differently than the other COVID-19 vaccines. It comprises a synthetically engineered version of the S protein and an adjuvant (i.e., saponin-based Matrix-M). The adjuvant signals the immune system to spring into action, thereby enhancing the immune response to produce large quantities of neutralizing antibodies. This technology is not new, as it has been effectively used for the hepatitis B (HepB) and human papillomavirus vaccines (HPV), but it does take longer to develop. The NVX-CoV2373 (Novavax) vaccine does not contain live virus particles, and thus, it cannot replicate or cause infection with COVID-19.  The vaccine demonstrated 89.3% efficacy in the UK phase 3 trial, which enrolled 15,000 participants between 18 and 84 years, including 27% over the age of 65.  In a report released on January 28, 2021, the NVX-CoV2373 (Novavax) is cited as the first COVID-19 vaccine to demonstrate clinical efficacy against the UK and South Africa variants. Data from South Africa’s phase 2b trial showed a 60% risk reduction against COVID-19 in a region when over 90% of cases are attributable to the prevalent South Africa COVID-19 variant (Novavax, 2021a). In the US and Mexico, the phase 3 PRE-fusion protein subunit Vaccine Efficacy Novavax Trial (PREVENT-19) is underway and has already enrolled more than 16,000 participants; it expects to achieve the targeted enrollment of 30,000 by mid-February 2021. PREVENT-19 is a randomized, placebo-controlled, observer-blinded study evaluating the efficacy of NVX-CoV2373 in adults aged 18 and older, including at least 25% of participants aged 65 and older (Novavax, 2021b). The vaccine requires a two-dose series, administered 21 days (3 weeks) apart. Participants from phase 1/2 trials endured minimal adverse effects, with the most common including injection site pain, muscle pain, fever, rash, and nausea. Data revealed no serious adverse events, and systemic reactions were mild (Keech et al., 2020).

References

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American College of Obstetricians and Gynecologists. (2021). Vaccinating pregnant and lactating patients against COVID-19. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/vaccinating-pregnant-and-lactating-patients-against-covid-19

American Society of Health System Pharmacists. (2021). Assessment of evidence for COVID-19-related treatments: Updated 01/29/2021. https://www.ashp.org/-/media/assets/pharmacy-practice/resource-centers/Coronavirus/docs/ASHP-COVID-19-Evidence-Table.ashx

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Centers for Disease Control and Prevention. (2020b). Immunization courses: Webcast and self-study. https://www.cdc.gov/vaccines/ed/courses.html#covid-19

Centers for Disease Control and Prevention. (2021). Interim clinical considerations for use of mRNA covid-19 vaccines currently authorized in the United States. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html

Johnson & Johnson. (2021a). Johnson & Johnson announces single-shot Janssen COVID-19 vaccine candidate met primary endpoints in interim analysis of its Phase 3 ENSEMBLE trial. https://www.prnewswire.com/news-releases/johnson--johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial-301218035.html

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