As of 08/2021
Study Title: Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial.
Study Title: Efficacy and Safety of mRNA-1273 SARS-CoV-2 Vaccine
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30. PMID: 33378609; PMCID: PMC7787219.
Study title:Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
Summary: This randomized controlled trial published by NEJM assess the safety and immunogenicity of two SARS-CoV-2 RNA candidate vaccines: BNT162b1 and BNT162b2. The researchers found that the BNT162b2 is safer and that both candidate vaccines present with a similar immunogenicity profile. Based on these findings, the BNT162b2 vaccine will be advanced to a pivotal phase 2-3 safety and efficacy evaluation.
Background: The purpose of this randomized controlled trial was to assess the safety and immunogenicity of the BNT162b1 and BNT162b2 SARS-CoV-2 RNA candidate vaccines in healthy adults aged 18 to 55 and 65 to 85 years old.
Methods: This is an ongoing placebo-controlled and double blinded phase 1 clinical trial being conducted in the United States. Vaccinated subjects are being assessed for two outcomes: safety and immunogenicity. Safety includes screening for vaccine-induced local and systemic side effects and adverse outcomes. Immunogenicity is the ability for an antigen to elicit an immune response that helps the body fight off infection. In short, immunogenicity assesses whether the vaccine is significantly effective in preventing COVID-19 infection. In total, 195 participants were randomized to either receive the placebo, the BNT162b1 vaccine, or the BNT162b2 vaccine. Moreover, participants receiving a COVID-19 candidate vaccine were injected with either a 10 μg, 20 μg, 30 μg, or 100 μg dosage. Also, most participants received two injections of their assigned dose with a 21-day interval between doses, except for those who received a 100 μg dose.
Results: The researchers have thus far concluded that the BNT162b2 candidate vaccine is safer due to showing a reduced risk of local and systemic side effects as compared to the BNT162b1 candidate vaccine, especially in those aged 65 to 85 years old. Both candidate vaccines exhibited similar dose-dependent immunogenicity in both the younger and older cohorts of adults. Specifically, IgG antibody response and virus neutralizing response was most maximal for participants administered the 10 μg to 30 μg doses. Also, immunogenicity was generally lower in the 65 to 85 year-old cohort than in the 18 to 55 year-old cohort. which is justified by the fact that aging dampens the body’s ability to generate an immune response. The researchers are still determining whether this data is statistically significant.
Conclusion: Based on the results, the researchers have enough evidence to advance the BNT162b2 candidate vaccine to a pivotal phase 2-3 safety and efficacy evaluation.
Study title: Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2:A preliminary report of a phase 1/2, single-blind, randomized controlled trial
Publication date: 07/20/20
Background: This phase 1/2, single-blind, randomized control trial tested the safety, side effects, and immunogenicity of a viral vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine that expresses the spike protein of SARS-CoV-2 called ChAdOx1 nCoV-19. Results were compared to the same parameters of the meningococcal conjugate vaccine called MenACWY, which served as the standard/control.
- A phase ½ randomized control trial is a study that tests:
o How well a disease responds to a new treatment compared to an accepted standard/control
o The safety of the new treatment
o Side effects of the new treatment
o Optimal dosage of a new treatment
- Single-blinded means that only the researcher(s) conducting the study know whether participants are receiving the experimental intervention (i.e. SARS-CoV-2 vaccine) or standard/control (meningococcal conjugate vaccine). The participants do not know which vaccine they received until after the trial is over.
- A viral vectored vaccine uses live viruses to carry viral DNA that encodes antigens into human cells. Antigens are foreign substances that elicit an immune response in the body. Thus, when viral DNA enters an infected human cell and expresses its antigens, the body will elicit an immune response to fight off the viral infection.
- Immunogenicity is the ability for an antigen to elicit an immune response that helps the body fight off infection.
- The SARS-CoV-2 spike protein helps the SARS-CoV-2 enter into human cells, hence the purpose of using it to design a viral vectored vaccine.
- The trials were conducted at 5 sites in the UK on 1,077 participants, 543 who received the experimental ChAdOx1 nCoV-19 vaccine and 534 who received the control MenACWY vaccine.
- Outcomes assessed included:
o Baseline and post-vaccination humoral immune responses using immunoassays
o Vaccine efficacy, measured by number of symptomatic and lab confirmed SARS-CoV-2 cases
o Vaccine safety, measured by number of vaccine-induced serious adverse events, was assessed 28-days post vaccination
- Minor vaccine-induced adverse reactions (i.e. pain, feverish, chills, muscle aches, headaches, fatigue) were more frequent in the ChAdOx1 nCoV-19 vaccine group, and such reactions could mostly be controlled via prophylactic medications.
- There were no recorded serious adverse events elicited by the ChAdOx1 nCoV-19 vaccine.
- The ChAdOx1 nCoV-19 induced a promisingly robust humoral immune response, especially after administration of a booster dose.
Conclusion: The ChAdOx1 nCoV-19 shows acceptable vaccine safety, as well as promising vaccine efficacy as presented by the vaccine’s ability to induce a robust humoral and cellular immune responses and likely limit COVID infection. These results support the need for progression of the ongoing ChAdOx1 nCoV-19 vaccine trials onto further phases.
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Publication date: 07/14/20
- Phase 1 clinical trial to evaluate the safety and efficacy of this vaccine
- What is a phase 1 clinical trial?
- Testing of the drug on healthy volunteers for safety; involves testing multiple doses
- Goal: Determines whether the drug is safe to check for efficacy
- What is a messenger RNA (mRNA)?
- mRNA definition: inside the human body, messenger RNA supplies the information that DNA uses to make proteins, which regulates our cells and tissues.
- Viruses use RNA for a more damaging purpose
- Viruses invade healthy cells and multiply within health cells, sometimes causing sickness or death
- Ex. The mRNA in COVID-19 enables a “spike protein” that pierces cells throughout the body. This is particularly damaging whenever the virus invades the lungs, making the simple act of breathing challenging
- What is a mRNA vaccine?
- An mRNA vaccine contains a synthetic (made in a laboratory) version of RNA that a virus uses to form proteins
- The vaccine does not contain enough genetic information to produce viral proteins; just enough to prime the immune system into thinking a virus is present so that it will spring into action to make antibodies.
- Antibodies are proteins specifically designed to fight a virus
- Making antibodies prior to actually being infected allows the body to have enough immunity to essentially block the virus from damaging the body
- 45 healthy adults, ages 18-55 years of age
- Each participant received 2 vaccinations, 28 days apart
- Three different dosages were tested
- 15 participants in each dose group
- After the first vaccination, antibody responses were higher with a higher dose
- After the second vaccination, the antibody levels were higher and detected in all participants
- Adverse events that occurred in more than half of the participants included:
- Pain at injection site
- Systemic adverse events were more common after the second vaccination, particularly with the highest dose.
- Three participants (21%) in the highest dose group on the second vaccination reported one or more severe adverse events
Conclusion: These safety and efficacy findings support advancement of this particular mRNA vaccine to later-stage clinical trials.