COVID-19, Vaccines, Prevention

by Editorial Board last updated 2021-03-02 19:36:05.376373-05:00
COVID-19 Vaccine

Approved Vaccines

Vaccine Pfizer-BioNTech COVID-19 Vaccine (Comirnaty, mRNA BNT162b2) Moderna COVID-19 Vaccine (mRNA-1273) Janssen COVID-19 Vaccine
Janssen/Johnson & Johnson
(Ad26.COV2.S)
COVID-19 Vaccine AstraZeneca
(AZD1222 or
ChAdOx1, Covishield (India)).
CoronaVac SinoVac Biotech Co. BBIBP-CorV.
Sinopharm/Beijing
Institute of Biological Products
Sputnik V (Gam-COVID-Vac)
Gamaleya Research
Institute
Authorized for Use in

USA, Canada, EU, UK, WHO EUL, Mexico, Singapore, Australia, Japan, Israel & over 60 others.



USA, Canada, EU, UK, Isreal, SIngapore & up to 10 others

USA, South Africa.

 

UK, EU, India, Australia, S. Africa, Mexico, S. Korea, Argentina, UAE & up to 15 others China, Brazil, Chile, Turkey, Indonesia China, Bahrain, UAE, Nepal, Peru, Hungary & a few others Russia, Belarus, UAE, Argentina, Mexico, Hungary, Iran & at least 15 others
Age

≥ 16 yrs. Trials for age 12-17 ongoing; 5-11
to start Q2, <5 to start Q4
(US EUA
for <12 years for any
vaccine not until Q2 2022)

≥ 18 yrs. Trials for age 12-17 yrs ongoing
(US EUA
for <12 years for any
vaccine not until Q2 2022)

≥ 18 yrs.Trials for age 12-17 yrs
ongoing
(US EUA
for <12 years for any vaccine not until Q2 2022)

≥ 18 yrs. Trials for age 6-17 yrs
starting
≥ 18 yrs ≥ 18 yrs ≥ 18 yrs
Type Lipid nanoparticle (LNP) encapsulated mRNA Lipid nanoparticle (LNP) encapsulated mRNA Non-replicating adenovirus vector Nonreplicating adenovirus vector Inactivated Inactivated Nonreplicating live
adenovirus
Overall efficacy vs. symptomatic disease 95% in Phase III; 94% in real life use in >1 million Israelis (doi:10.1056/NEJMoa2110165) 94.1% 72% (US trial); 66.9% (US,Brazil,
South Africa combined); 64% in
South Africa where 95% of cases
were B.1.351
62%based on UK approval. Other heterogeneous results from multiple combined trials now published  50-78% (non peer reviewed)  73.9% (Chinese
government press
release only)
 91.4%
Efficacy Age >65 94.7% 86.4% 66.10% Insufficient data  No data  No data  No data
Efficacy vs. severe disease or death 100% (preliminary) 100% (preliminary) 85.4% vs severe/critical; 100%
against death after  day 28 based
on 7 deaths in placebo group
100% (preliminary)  No data  No data 100% (press release data)
Efficacy vs. asymptomatic infection (does not equal transmission) Unknown. 90% in asymptomatic infection; proxy data from Israel Asymptomatic PCR positivity in 0.1% of vaccines at day 28 74.2% against asymptomatic
seroconversion at day 71 (not
serial PCR)
Unknown  No data  No data  No data
Duration of efficacy after final dose Unknown  Unknown Unknown Unknown  No data  No data  No data
Dosing 0.3 mL IM; 2 doses 21 days apart (up to 42 days acceptable). No further boosters
currently recommended
0.5 mL IM; 2 doses 28 days apart (up to 42 days acceptable). No further
boosters currently recommendeded
0.5 mL IM; 1 dose (2 dose trial in progress) 0.5 mL IM; 2 doses 4-12 wks apart (UK & EU) 2 doses 14 or 28 days apart 2 doses 14 or 21 days apart 2 doses 21 days apart.
Dose 1 is Ad26, Dose 2 Ad 5
Storage -70°C (-94°F) or 2-8°C (36-46°F) for up to 5 days (may include transportation at this temp for up to 12 hrs). New data on 2-week storage at -25°C under PDA review. -20°C (-4°F) for up to 6 mos 2-8°C (36-46°F) for up to 30 days 2-8°C (36-46°F) for up to 3 mos
(for shipping and use); -20°C (-4°
F) for up to 2 yrs
2-8°C (36-46°F)  2-8°C (36-46°F) 2-8°C (36-46°F) -18°C (0°F) for up to 6 mos; 2-8°C (36-46°F) for up to 30 days
Contraindications Anaphylaxis or immediate allergic reaction (within 4 hours of administration) to a
previous dose of an mRNA vaccine or separately to a vaccine constituent including polyethylene glycol (PEG) or polysorbate. Defer vaccination for 90 days after receipt of monoclonal or plasma
therapy.
Same as Pfizer mRNA Same as Pfizer and Moderna mRNA, except J&J has only polysorbate constituent Anaphylactic reaction to a
vaccine constituent
 No data  No data  No data
Precautions Immediate allergic reaction (within 4 hours of administration) to any other vaccine or injectable therapy not related to a component of mRNA-COVID-19 vaccines
or polysorbate. Persons with a reaction to a vaccine or injectable therapy that contains multiple components, one of which is PEG, another mRNA vaccine component or polysorbate, but in whom it is unknown which component elicited the immediate allergic reaction
Same as Pfizer mRNA Same as mRNA plus persons with a contraindication to mRNA COVID-19 vaccines (including
allergy to PEG) have a precaution to the Janssen/J&J vaccine (cross-reactive polysorbate 80) and vice-versa.
Postpone vaccination in persons
with acute severe febrile illness.
No data  No data  No data
Not contraindications Allergies: food (including egg and gelatin), pet, insect, venom, environmental, latex, oral
medications (including the oral
equivalents of injectable medications); any other history of anaphylaxis not related to vaccine or injectables; or a family history of anaphylaxis
Same as mRNA Same as Pfizer and Moderna mRNA    No data  No data  No data
Adverse effects Anaphylaxis 4.7 per million doses; 90%
within 30 minutes, 96% females. V-safe data: injection-site pain (71%), fatigue (33.5%), headache (30%), myalgia (23%), fever (11%). Reaction rates were much higher for dose 2, day 1 (Pfizer data only): injection-site pain (79%), fatigue (53%), headache (43%), myalgia (47%), fever
(29%). VAERS: 640 SAE's reported in first
13.6 million doses of mRNA vaccines
Anaphylaxis: 2.8 per 1 million doses; 90% within 30 minutes; 96% females. V-safe data: injection-site pain (71%), fatigue (33.5%), headache (30%), myalgia (23%), fever (11%). Reaction rates were much
higher for dose 2, day 1 (Pfizer data only): injection-site pain (79%), fatigue (53%), headache (43%), myalgia (47%),
fever (29%). COVID arm: up to 6 inch diameter rash at injection site 5-10 days after vaccination. VAERS: 640 SAE's
reported in first 13.6 million doses of
mRNA vaccines
No data yet on anaphylaxis, none
in trials, contains polysorbate 80
related to PEG. Injection-site
reactions (pain), fatigue, headache, fever, and weakness
Injection-site pain, fatigue,
headache, fever, and weakness
 No data  No data  No data
Pregnancy Use. No reproductive or development concerns (preliminary); risk of disease effect > known vaccine risk; endorsed for use by ACOG. No reported issues in 20,000 pregnancies to date in the USA Same as Pfizer mRNA Use. No reproductive or
development concerns (preliminary); risk of disease effect > known vaccine risk;
endorsed for use by ACOG.
Unknown  No data  No data  No data
Immunocompromised or HIV Use, but potential for reduced immune
response and unknown safety and efficacy
profiles exist in this group. Initial safety in
solid organ transplant recipients (n = 200;
preliminary). Consider delaying dose 2
until 6 wks if better immune function
expected at that time.
Use, but potential for reduced immune
response and unknown safety and
efficacy profiles exist in this group.
Initial safety in solid organ transplant
recipients (n = 200; preliminary). Consider delaying dose 2 until 6 wks if better immune function expected at that
time.
Use, but potential for reduced immune response and unknown safety and efficacy profiles exist in this group. Initial safety in solid organ transplant recipients (n = 200; preliminary). Consider delaying dose 2 until 6 wks if
better immune  function expected at that time.
Insufficient data  No data  No data  No data
References

FDA Provider Fact Sheet / EUA Prescribing Information

N Engl J Med 2020; 383:2603

FDA Provider Fact Sheet / EUA Prescribing Information

N Engl J Med DOI: 10.1056/NEJMoa2035389

FDA Provider Fact Sheet (27 Feb 2021) here

EMA Authorization (29 Jan 2021) & Fact Sheet (18 Feb 2021) here     Phase III randomized trial data: Lancet 2 Feb 2020
Interchangeability with other COVID vaccines No data; use same vaccine for all doses. If dose of 1 brand is unavailable, any available mRNA vaccine may be administered for dose 2 at a minimum interval of 28 days and constitutes a complete series No data; use same vaccine for all doses. If dose of 1 brand is unavailable, any available mRNA vaccine may be administered for dose 2 at a minimum interval of 28 days and constitutes a complete series No data, do not interchange. If 1
dose of an mRNA is followed ≥ 28 days later with  Janssen / J&J vaccine (subsequent to a contraindication issue) consider
as a valid, completed single-dose Janssen/J&J primary vaccination
No data, use same vaccine for all
doses
 No data  No data  No data

Background / General Considerations

  • Bottom-line vaccination messaging for the three vaccines currently approved in the US (Pfizer, Moderna, Janssen/J&J) is that each: 1) effectively eliminates the risk of COVID-19 death; 2) nearly eliminates the risk of hospitalization; 3) significantly reduces the ability to infect somebody else (preliminary); and that 4) two doses are highly effective against both B.1.1.7 and B.1.351 variants (preliminary).
    • Current vaccine scorecard:  291 candidates, 70 in clinical trials, 20 in Phase III.  Table lists those in current use in at least 1 country. All vaccines express similar antigenic components related to the original SARS CoV-2 strain isolated in China.
    • Efficacy data including for subgroups are not strictly comparable between vaccines as studies were carried out at different phases of the pandemic, with different population profiles and in different countries
  • Current vaccine preference order:
    • Vaccines of choice: 2-dose mRNA vaccines (Pfizer/BioNTech/Moderna), single-dose refrigerator stable adenovirus vaccine Janssen/J&J
      • Janssen/J&J vaccine may be less effective against all symptomatic disease in persons >60 yrs with co-morbidities
    • Alternate vaccines: AstraZeneca (effectiveness against B.1.351 variant unproven)
    • Vaccines without regulatory approval by a major agency:   Sinovac, Sinopharm, Gamaleya

Advanced Pipeline

  • A 2-dose NVX-CoV2373 (Novavax; protein) vaccine candidate was reported by press release to have efficacy of 89.3% against mild, moderate, or severe disease with onset at least 7 days after the second study vaccination (21 days later) in serologically negative (to SARS-CoV-2) adult participants at baseline. The US trial to be submitted to FDA is expected to complete enrollment in mid-February. The vaccine is stable at conventional refrigerator temperatures for up to 6 months and at room temperature for 24 hours. EUA expected in April.
  • In a UK trial of the Novavax vaccine efficacy was 95.6% against the original SARS-CoV-2 strain and 85.6% against the B.1.1.7 strain. Both Novavax vaccine and Johnson & Johnson vaccine candidates in Phase 3 trials had lower efficacy (50%–60%) against B.1.351 strain but appeared highly protective against severe disease and death in South Africa.

Comments

  • RNA vaccines have the greatest ability for rapid, large-scale manufacturing (scale-up) and greater flexibility for antigen replacement with little lead time. 
  • Viral vector vaccines have a high level of protein expression, stability, and strong immune responses; adenovirus vectored vaccines are cheap and rapid to produce at scale.
  • Recombinant protein technology is widely used for many existing diseases;  lots of experience and safety record and much existing production capacity but with longer production times.
  • SARS-Cov-2 experienced persons: high-quality studies indicate that previously SARS-CoV-2–infected persons have an equal or better antibody response after 1 dose of mRNA vaccine when compared to persons who received 2 doses but had not had SARS-CoV-2 infection. Analysis of corresponding clinical trial data is underway, but almost certainly 1 vaccine dose appears adequate for those with previous COVID-19. Practicalities concerning the verification of previously documented infection during rapid vaccine rollout.  However, US authorities have yet to approve this approach in the absence of clinical efficacy data, and also argue that the correlates of protection by given levels of antibody are still unknown; many experienced clinicians feel strongly that eventual clinical data will support this approach. 
  • Delayed second dose for 2-dose vaccines:  US authorities remain strongly opposed to delaying the second dose of an mRNA vaccine or using a single dose of an mRNA vaccine for persons previously infected. One dose in an unvaccinated person, even with a lower nAb response, could be protective against the standard SARS-CoV-2 strain but not against novel variants and the duration of immunity after a single dose is unknown. In addition, nAb did not show large increases until after receipt of the 2nd dose (both Pfizer and Moderna). 
    • a post-hoc exploratory analysis of 4 mixed clinical trial datasets from subjects given the AstraZeneca vaccine that suggests that a more prolonged interval to the second dose, up to 3 months, is beneficial for the immune response and efficacy provides reasonable confidence of a delay for this vaccine which has lesser efficacy overall than mRNA vaccines.
  • Quarantine and vaccination:  vaccinees do not need to quarantine after a SARS-CoV-2 exposure for the next 90 days after a complete 2 dose series.  Persons already in quarantine because of an exposure should not be vaccinated until quarantine is over.
  • Additional considerations
    • Antibody testing is not recommended to assess for immunity following COVID-19 vaccination or to assess the need for vaccination in an unvaccinated person; no correlates of protection are available and the wide variety of antibody assays have variable targets (not all related to vaccine response) and performance.  Consider in patients whose ability to mount a B-cell response is uncertain such as transplant recipients and people on anti-B cell therapies.
    • Prevaccination prophylactic use of antipyretic or analgesic medications (e.g., acetaminophen [paracetamol] or NSAIDs) to prevent postvaccination symptoms is not recommended because the impact on mRNA COVID-19 vaccine-induced antibodies is unknown. However, these medications may be used to treat postvaccination local or systemic symptoms.
    • Persons with recent (time period now undefined) documented acute symptomatic or asymptomatic SARS-CoV-2 infection should be vaccinated but may choose to temporarily delay vaccination (conserves doses for others), if desired. Risk of reinfection likely increases with time following initial infection.  In acute illness, including for those who develop SARS-CoV-2 infection after the first vaccine dose but before receipt of the second dose, vaccination should be deferred until criteria for discontinuing isolation have been met
    • Currently available vaccines are not recommended for outbreak management or for postexposure prophylaxis (vaccination to prevent the development of SARS-CoV-2 infection in a person with an exposure).
    • The majority of persons are protected by 12 days after the first dose but this single-dose immunity may well be very transient without a second dose; this could not be assessed one way or the other because all trial subjects eventually received a second dose.
    • If Dose 2 is administered no more than 4 days before the minimum (21 or 28 day) interval it is considered valid; however, a dose inadvertently administered > 4 days before the minimum interval does not need to be repeated.
    • Should be given at least 14 days apart from any other vaccine, but shorter intervals may be used where the benefits of the other vaccine outweigh the potential unknown risks and neither vaccine needs to be repeated.
    • Do not have a risk of modifying the vaccine recipient’s genetic makeup as mRNA does not enter cell nucleus where host DNA is located.  Adenovirus vaccine DNA in the nucleus has deletions of critical genes therefor cannot replicate and cannot integrate into DNA. 
  • Further detail:  https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/