COVID-19, Vaccines

by David O. Freedman, M.D. last updated 2022-07-30 11:54:04.918421-04:00 © Antimicrobial Therapy, Inc.
COVID-19 Vaccines, Vaccination Schedules

Vaccine Preferences (US)

  • Vaccine information is divided into summary tables for US and WHO authorized vaccines and individual vaccine pages. See below. For complete information covering vaccine doses, efficacy, adverse effects, and mix and match dosing considerations for primary and booster doses: see Pfizer, Moderna, Janssen/J&J, NovavaxAstraZeneca, SinoPharm, Sinovac, Sputnik, Bharat.
  • Vaccine Efficacy (VE) Against the Omicron Variants
    • VE based on breakthrough infections and hospitalizations in the Omicron era is increasingly difficult to calculate due to the variability in vaccine types, numbers of doses, and spacing of doses in the general population, and due to the decentralized data collection mechanisms especially for cases confirmed by self-tests in countries with federal structures (including the US).
    • Available observational and laboratory-based data (neutralizing titers) continue to support the need for triple vaccination in those with no history of prior infection.
    • For Omicron, 3-dose VE is more than 95% against hospitalization, more than 95% against death, and approximately 50% against symptomatic infection. In marked contrast, 2-dose VE is approximately 50% against hospitalization, 60% against death, and no more than 25% against symptomatic infection. 
    • The duration of vaccine efficacy in triple vaccinated persons remains unclear, but T-cell immunity which protects against severe disease appears to last at least 6 months.
    • Recipients of 2 doses of mRNA vaccine appear to have zero or minimal neutralizing antibody titers against Omicron
      • booster doses of non-mRNA vaccines are unproven in preventing population transmission with Omicron and transmission rates appear independent of vaccination status.
  • Bottom-line vaccination messaging for the three vaccines currently approved in the US :
    • Only mRNA vaccines (Pfizer, Moderna) or Novavax should be use
    • Novavax is a recombinant protein sub-subunit, adjuvanted vaccine made by conventional production as per most vaccines (eg HepB); with mRNA vaccines the recipient's body makes the same SARS-CoV-2 protein after injection of the mRNA
      • Janssen/J&J is last resort and for uncommon situations due to wide availability of mRNA vaccines and complete absence of life-threatening adverse effects
      • In resource limited environments Janssen/J&J vaccine with ease of storage will still save lives when other vaccines not available.
    • Three doses of mRNA vaccine or a heterolgous adenovirus then mRNA series are the only current effective strategies against the Omicron variant; prior COVID infection likely can substitute for 1 of the 3 vaccines doses.
    • The third vaccine dose in immunocompromised persons is not a booster but rather an additional primary dose to induce initial immunity in those unable to achieve it in the first place.
      • Doses 4 and 5 as a booster in the immunocompromised population is  recommended.
  • Against pre-Omicron SARS-COV-2 variants, substantial data indicate that the Moderna vaccine has both a VE and durability advantage over the Pfizer vaccine (likely due to the higher mRNA dose in the primary series), and that a single dose of Janssen/J&J vaccine, which is no longer a preferred vaccine in the US is inadequate. Comparison data after the 3rd dose (6-month booster) of mRNA vaccines are not yet available
    • Adenovirus vaccines are progressively less favored by guideline making bodies in countries where supplies of mRNA vaccines are ample.

Authorized Vaccines

U.S. CDC COVID-19 Vaccination Schedules

CDC COVID-19 Vaccine Schedule - Most People

CDC COVID-19 Vaccine Schedule - Immunocompromised

Reference: At-A-Glance COVID-19 Vaccination Schedules (CDC)

U.S. FDA Authorization

  • The following COVID-19 vaccines have U.S. FDA authorization
  • See individual vaccine pages for complete summaries: Pfizer, Moderna, NovavaxJ&J
    • Pfizer, Moderna, Novavax are equally vaccines of choice for a primary series but only Pfizer and Moderna are authorized for booster doses.  
  • Janssen/J&J vaccine is now considered second line only to be used in extenuating circumstances
  • A mixed primary series of an mRNA vaccine followed by Novavax is not recommended at this time, but if done is considered a fully primary series.

 Up to Date Status

  • CDC Definition of "Up to date".  A person aged ≥ 6 months who has received all recommended primary COVID-19 vaccine doses (including an age-appropriate additional primary dose for immunocompromised persons when eligible) as well as recommended age-appropriate booster doses (1 or 2) when eligible. However, persons aged 18-49 years who received a Janssen/J&J vaccine dose for both the primary and booster dose are considered to be up to date. Such persons may nevertheless get a second optional booster dose with an mRNA vaccine if desired.  Up to date status alone affects recommendations for quarantine/isolation. 

WHO Authorization

  • The following COVID-19 vaccines have WHO and may have other regulatory authorization
  • These vaccines also satisfy U.S. vaccination requirements for entry into the United States
  • See individual vaccine pages for complete summaries: AstraZeneca, SinoVac, SinoPharm, Bharat
  • Cansino (Convidecia) vaccine is only available in China and a few Asian countries.
    • Ad5.CoV2-S vectored recombinant single-dose (0.5 ml) approved only for ages >18 yrs.  VE of 58% against symptomatic infection and 92% against severe disease with ancestral strain virus in trials.

EUL Vaccines

(Pfizer, Moderna, Janssen, Astrazeneca, Sinovac, Sinopharm, Bharat, Novavax, Cansino)

AstraZeneca COVID-19 Vaccine 
(Vaxvevria, Covishield (India), AZD1222,
ChAdOx1).
SinoVac COVID-19 Vaccine (CoronaVac) Sinopharm/Beijing
Institute of Biological Products COVID-19 Vaccine (BBIBP-CorV)
Bharat COVID-19 Vaccine (Covaxin). FDA rejected EUA application for pediatric use. Novavax COVID-19 Vaccine (Nuvaxovid, Covovax (India), NVX-CoV2373). 
  See vaccine page for full details See vaccine page for full details See vaccine page for full details See vaccine page for full details See vaccine page for full details
Age ≥ 18 yrs. Trial for age 6-17 yrs currently paused. Many countries not using in adults under 60 due
to thrombosis AE.
≥ 18 yrs ≥ 18 yrs ≥ 18 yrs  ≥ 18 yrs
Type Nonreplicating chimpanzee adenovirus vector Inactivated Inactivated Inactivated  Recombinant protein subunit
Primary Dosing in adults (including immunocompromised; including additional primary dose
0.5 mL IM; 2 doses 4-12 wks apart (UK & EU) and 4 wks in US trial. 8-12 wks under WHO EUL 2 doses 14 or 28 days apart 2 doses 14 or 21 days apart 2 doses 28 days apart  2 doses 21 days apart
Booster Dosing (WHO EUL guidelines presented; wide national variations regarding boosters)

Booster at 4-6 months after dose 2. Consider EUL mRNA vaccine for 2nd primary or subsequent booster doses.

Booster at 4-6 months after dose 2. Consider EUL mRNA or vectored vaccine for 2nd primary or subsequent booster doses.  Booster at 4-6 months after dose 2. Consider EUL mRNA or vectored vaccine for 2nd primary or subsequent booster doses.  Booster at 4-6 months after dose 2. Consider EUL mRNA or vectored vaccine for 2nd primary or subsequent booster doses.  Booster at 4-6 months after dose 2. Consider EUL mRNA or vectored vaccine for 2nd primary or subsequent booster doses. 

Development Scorecard

  • Current vaccine scorecard
    • 353 candidates, 135 in clinical trials, 39 in Phase III.  32 in use in at least 1 country. Tables above list those in current use in multiple countries or with authorization from FDA, EMA, or WHO EUL.
      • All current vaccines express similar antigenic components related to the original SARS CoV-2 strain isolated in China.  Three doses of mRNA vaccines clearly induce neutralizing antibody effective against all known variants. 
      • Modified bivalent vaccines from Pfizer and Moderna that include antigenic determinants derived from the Omicron BA.1 variant have been shown in small studies to significantly boost neutralizing titers against BA.1 in previously triple mRNA vaccinated persons.  Titers in these persons are 3 fold less against BA.4/5 variants.  
        • FDA is recommending production and use of a bivalent original strain/BA.5 mRNA vaccine for the 2022-23 winter season (no data yet); supply is unlikely prior to late 2022.

Advanced Pipeline

  • A preliminary analysis (press release) indicates that 1 booster dose of a candidate adjuvanted recombinant protein vaccine targeting the original SARS-CoV-2 parent strain virus (Sanofi/GSK joint venture) given between 4 and 10 months after a complete primary vaccination schedule of another vaccine elicited a 9- to 43-fold range increase in nAbs for all age groups tested (n = 521). Results were similar whether the primary vaccine received was AstraZeneca, Janssen/J&J, Moderna, or Pfizer.
  • Some investigators believe that a heterologous boost with a conventional recombinant protein vaccine after priming with either an mRNA vaccine or an adenovirus-vectored vaccine may provide a more long-term immune response (eg Novavax or Sanofi/GSK). Novavax has been shown in 1 trial of heterologus boosting of mRNA vaccine to produce a robust booster in antibody titers. A Phase 3 trial of this vaccine candidate as a 2-dose primary series showed 90% protection against symptomatic disease in the pre-delta era only.  Bivalent Novavax vaccine is in development.  Final FDA authorization of ancestral strain Novavax vaccine is pending final approval of manufacturing facilities in India by the FDA

Comments

  • Special situations for compromised persons who have missed additional primary doses
    • mRNA vaccines: For persons who inadvertently received the booster dose before their third primary dose, regardless of type of vaccine received as the booster dose, administer a Pfizer vaccine or a Moderna vaccine (100 µg) as the fourth dose (third primary) at least 3 months after the third dose. 
    • Many recipients of Janssen/J&J vaccine may have received a booster dose (Pfizer, Moderna [50 µg], or Janssen/J&J vaccine), without having had the second (additional) mRNA vaccine dose. In this situation, regardless of type and timing of vaccine received as the second dose, administer a Pfizer vaccine or a Moderna vaccine (100 µg) as the third (additional) dose at least 2 months after dose 2. 
  • Quarantine and vaccination: 
    • No quarantine (applies to exposed persons fully up-to-date on vaccination) is recommended for the following persons, but they should test on day 5; if the test result is positive or symptoms develop, they should isolate;
      • Aged ≥ 18 years and received all recommended COVID-19 vaccine doses
      • Aged 5-17 years and completed a COVID-19 primary vaccination series
      • Any aged persons with confirmed COVID-19 within the past 90 days (positive viral test result); no test recommended on day 5.
    • 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. 
      • With no correlate of immunity; +ve IgG only minimally reassuring, -ve IgG unhelpful in patients whose ability to mount a B-cell response is uncertain such as transplant recipients and people on anti-B cell therapies.
    • Persons with recent (time period now undefined) documented acute symptomatic or asymptomatic SARS-CoV-2 infection should be vaccinated.
      • 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 post-exposure 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.
    • 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.
    • Other non-COVID vaccines notably influenza vaccine may be administered simultaneously with or at any interval before or after any SARS-CoV-2 vaccine dose.
    • Orthopoxvirus vaccination: Myocarditis may occur after ACAM2000 orthopoxvirus vaccine or mRNA (i.e., Moderna and Pfizer-BioNTech) or Novavax COVID-19 vaccines; the risk is unknown for JYNNEOS
      • Particularly adolescents or young adult males, might consider waiting 4 wks after orthopoxvirus vaccination before receiving a Moderna, Novavax, or Pfizer-BioNTech COVID-19 vaccine. However, during outbreaks, orthopoxvirus vaccination should not be delayed 
    • mRNA vaccines 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 therefore cannot replicate and cannot integrate into DNA. 
  • Further detail:  https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/

Related Topics

  • For pre- and post-exposure prophylaxis, see COVID-19 Prophylaxis
  • For treatment and other aspects of COVID-19 management, see COVID-19, SARS CoV-2