Just a little more than a year after the United States reported its first case of coronavirus disease 2019 (COVID-19), there have been more than 27 million cases and more than 460,000 deaths in the US, according to the Centers for Disease Control and Prevention.1
Lockdowns, travel restrictions, masking, and social distancing were not enough to contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its strain on the healthcare system. The focus of the outbreak has turned from containment to prevention through vaccination.
Traditionally, vaccines contain weakened or inactivated microorganisms, fragments of microorganisms, or genetic material from microorganisms that the immune system uses to produce a protein that elicits an immune response, thus producing antibodies.2
The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, utilizes messenger ribonucleic acid (mRNA) of the spike protein for SARS-CoV-2.3-5 The mRNA is contained within lipid nanoparticles, which allow the mRNA to enter cells.3-5 Once inside the cell, the mRNA is released and transcribed into the SARS-CoV-2 spike protein.4 This protein migrates to the cell surface, triggering a T-cell–mediated immune response against the spike protein.4 Immune activity against the spike protein hinders SARS-CoV-2’s ability to attach to host cells. Because the mRNA does not remain viable in the cell for very long, it cannot become a permanent part of the host cell.4
Normally, vaccines undergo years of rigorous research and testing. In extenuating circumstances, such as the COVID-19 pandemic, companies may apply for an Emergency Use Authorization (EUA) to expedite vaccine availability prior to full FDA approval. The process of issuing an EUA involves 6 key steps (Figure 16,7), which requires the FDA to determine that the benefits of the product outweigh its risks and that the product is appropriately efficacious.8 The WHO also has an Emergency Use Listing (EUL) that allows countries to expedite their own approval process for the new agent, as well as allowing UNICEF and the Pan American Health Organization to obtain the agent for distribution to countries in need.9 Prior to approval, Pfizer-BioNTech was required to provide at least 2 to 3 months of follow-up data postsecond-dose administration to gauge the vaccine’s safety and efficacy. This allowed sufficient time for immune-mediated allergic reactions and other adverse events (AEs) to manifest, as well as sufficient time to detect waning protection generated by IgM and IgG antibodies against the virus.8 The FDA issued an EUA for the BNT162b2 vaccine on December 11, 2020, and the WHO issued an EUL on December 31, 2020.
A phase 1 trial of BNT162b2 at a dose of 30 mcg, delivered in a 2-dose series separated by 21 days, determined the dosage had an acceptable amount of reactogenicity per AEs and sufficient antibody titers (ie, immunogenicity) against SARS-CoV-2.10 This vaccine then was tested in a phase 3 trial that randomized participants 1:1 to receive either BNT162b2 or placebo.11 Participants were included if they were at least 16 years of age and were either healthy or had stable chronic medical conditions, including HIV, hepatitis B, and hepatitis C. Individuals were excluded if they were pregnant or breastfeeding, had a medical history of COVID-19, were immunocompromised, or were actively receiving immunosuppressive therapy. The primary safety end points were solicited and unsolicited AEs within 7 days of each dose through 6 months post dose (nonserious AEs, 1 month postsecond dose; serious AEs, 6 months postsecond dose). The primary efficacy end points were efficacy against confirmed COVID-19 with the onset at least 7 days post second dose and efficacy in participants with and without evidence of prior infection. Secondary efficacy end points included efficacy against severe COVID-19 infection.
A total of 37,706 participants were enrolled, with 18,860 receiving at least 1 dose of the BNT162b2 vaccine (Figure 211). Baseline characteristics were similar between groups, with 42.2% of the population older than 55 years (Table 111). Localized reactogenicity was evaluated in 8183 participants within 7 days after the injection. Systemic reactogenicity was evaluated in the entire cohort and most often began within 1 to 2 days post vaccination and resolved within 24 hours of symptom onset, with more common and severe reactions occurring after the second vaccine dose. Fatigue and headache were the most commonly reported AEs, with fever occurring more frequently after the second dose (Table 211). Notably, lymphadenopathy occurred in 64 (0.3%) participants in the vaccine group compared with 6 (<0.1%) participants in the placebo group. Additionally, there were 4 reports of Bell’s palsy occurring within the vaccine group; however, this incidence rate is consistent with the rate in the nontrial population. No COVID-19–related deaths occurred in either group.
The efficacy rate between the first and second doses was 52%, which then climbed to 91% within the first 7 days post second dose. Ultimately, 95% efficacy rate was achieved post second dose for participants who had no evidence of existing or prior COVID-19 infection, 94.6% efficacy rate was achieved post second dose for participants with and without evidence of prior COVID-19 infection, and 88.9% efficacy rate was achieved post first dose for preventing severe COVID-19 infection.
Additional research of efficacy is ongoing against newly discovered viral variants, including the UK variant (B.1.1.7), the South Africa variant (B.1.351), and the Brazil variant (P.1). These variants are able to transmit more readily and may be able to better evade the immune system (Table 312-19). Laboratory testing suggests BNT162b2 produces a sufficient immune response to B.1.1.7 and B.1.351; however, activity against B.1.351 was lower in comparison with other SARS-CoV-2 variants.16 In a phase 1/2 trial in Germany (NCT04380701), BNT162b2 efficiently neutralized 19 pseudoviruses, indicating that the vaccine could remain efficacious against a variety of mutations.20 Unfortunately, investigators currently do not have enough data to know when changes to the BNT162b2 vaccine need to occur.
However, as of February 14, BNT162b2 has been authorized or approved for emergency use for individuals 16 years and older in 57 countries.21 This vaccine continues to be studied in different populations limited or excluded in the original trial, and investigators are following up on participants enrolled in the original trial. Additionally, Pfizer and BioNTech are working on developing a third “booster” vaccine to be given 6 months to a year after the second dose.22 They also are working on a process that will allow faster development (eg, 6 weeks) of vaccine derivatives to better combat the current and future variants.23
Jamie Wagner, PharmD, BCPS, is a clinical assistant professor at the University of Mississippi School of Pharmacy and an antimicrobial stewardship pharmacist at St Dominic Hospital in Jackson. She is immediate past chair of the Society of Infectious Diseases Pharmacists (SIDP) Antimicrobial Stewardship Committee, a member of the SIDP Strategic Planning Committee, and a member of the American College of Clinical Pharmacy ID PRN Research Committee.
Ryan Imel, PharmD, BCPS, is a 2012 graduate from Southern Illinois University Edwardsville School of Pharmacy. He is a clinical pharmacist lead at Memorial Hospital Shiloh in Shiloh, Illinois.