Issue 1,635: June 2, 2022
Ask the Experts: Answers Questions
about Adult Hepatitis B Vaccination and
COVID-19 Vaccines

As an additional service to IZ Express readers, we periodically publish special editions such as this one, providing you with new and updated Ask the Experts questions and answers from’s experts. This issue includes 9 Q&As about hepatitis B vaccination based on the new ACIP recommendations for vaccination of all adults through age 59 years, published April 1, 2022.
In addition, we have included 6 questions from’s Ask the Experts COVID-19 vaccination Q&As, last updated on May 24, 2022. Because COVID-19 vaccination recommendations and clinical guidance are updated frequently, reminds our readers to visit CDC’s web page “Use of COVID-19 Vaccines in the United States Interim Clinical Considerations” regularly.
You can find all of these Q&As and more than a thousand other Q&As about vaccines and vaccine administration on our "Ask the Experts" gateway page at's team of experts includes Kelly L. Moore, MD, MPH (team lead), Carolyn B. Bridges, MD, FACP, and Iyabode Beysolow, MD, MPH.

Adult Hepatitis B Vaccination Questions

Q: Which adults should receive hepatitis B vaccine (HepB)?

A: In general, one HepB series is needed in a lifetime, with rare exceptions described at the end of this answer.
As of April 2022, CDC recommends HepB vaccination of adults in the following groups:

  • All adults through age 59 years
  • All adults age 60 years and older with risk factors for hepatitis B:
    • People at risk for infection by sexual exposure
      • Sex partners of people testing positive for HBsAg
      • Sexually active people who are not in a long-term, mutually monogamous relationship (e.g., those with more than one sex partner during the previous 6 months)
      • People seeking evaluation or treatment for a sexually transmitted infection
      • Men who have sex with men
    • People at risk for infection by percutaneous or mucosal exposure to blood
      • People with current or recent injection drug use
      • Household contacts of people testing positive for HBsAg
      • Residents and staff members of facilities for people with developmental disabilities
      • Healthcare and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids
      • People on maintenance dialysis, including in-center or home hemodialysis and peritoneal dialysis, and people who are predialysis
      • People with diabetes, at the discretion of the treating clinician
    • Others
      • International travelers to countries with high or intermediate levels of endemic hepatitis B virus (HBV) infection (HBsAg prevalence of 2% or higher)
      • People with hepatitis C virus infection
      • People with chronic liver disease (including, but not limited to, people with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase or aspartate aminotransferase level greater than twice the upper limit of normal)
      • People with HIV infection
      • People who are incarcerated
  • Adults age 60 or older years without known risk factors for HBV infection may receive HepB vaccination

The official CDC recommendations for HepB vaccination of adults are available at has developed a standing order template for adult HepB vaccination:  
In general, people who have documented completion of a HepB series at any point or who have a history of previous HBV infection should not receive additional HepB vaccination, although there is no evidence that additional vaccination is harmful. In settings where the patient population has a high rate of previous HBV infection, prevaccination testing, which may be performed at the same visit when the first dose of vaccine is administered, might reduce costs by avoiding complete vaccination of people who are already immune. However, prevaccination testing is not required and should not create a barrier to vaccination.
Revaccination may be indicated for certain high-risk adults, including healthcare workers who are documented non-responders to an initial HepB series, and certain people who receive dialysis or who are immunocompromised. For specific revaccination guidance, see the 2018 ACIP recommendations for the prevention of hepatitis B at (pages 23–24).

Q: Where can I locate CDC's recommendations for HepB vaccination?

A: The most recent comprehensive recommendations for HepB vaccination were published April 1, 2022. The document is available at  
In addition to the published recommendations, CDC has produced a frequently asked questions page for HBV infection and HepB vaccination:

Q: Which HepB products can be given to adult patients?

A: PreHevbrio (VBI, 3-dose series), Heplisav-B (Dynavax, 2-dose series), and Twinrix (GSK, combination HepA-HepB, 3-dose series) are approved for adults age 18 years and older. Engerix-B (GSK) and Recombivax HB (Merck), both administered as a 1.0 mL 3-dose series, are approved for adults age 20 years and older; young adults who are age 19 receive the 0.5 mL pediatric dose of Engerix-B and Recombivax HB.

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Q: Please provide information about the newest product option for adult HepB vaccination, PreHevbrio.

A: PreHevbrio (VBI) was approved by the FDA in November 2021 for people age 18 years and older. It is a triple-antigen (containing S, Pre-S1, and Pre-S2 HBV surface proteins) recombinant vaccine produced in mammalian cells (Chinese hamster ovary cells), and containing an alum adjuvant. It is given intramuscularly in a 3-dose series of 1.0 mL (10 mcg) doses administered on a 0-, 1-, and 6-month schedule. The most common side effects of vaccination are injection site pain and tenderness, as well as fatigue, muscle aches, and headache.
PreHevbrio was approved based on clinical trials conducted in adults age 18 years and older that compared seroprotection rates (SPR, defined as anti-HBs of 10 mIU or higher, and indicative of protection against HBV infection) following 3 doses of PreHevbrio to rates following 3 doses of Engerix-B (GSK). The SPR for PreHevbrio among adults age 18 years or older ranged from 83.6% to 99.2% (overall, 91.2% for all adults) compared to Engerix-B, which ranged from 64.7% to 91.1% (overall, 76.5% for all adults).
PreHevbrio was included as an option for HepB vaccination of adults age 18 years or older in the current ACIP recommendations published on April 1, 2022:  
The package insert for PreHevbrio is available here:

Q: Please explain the HepB vaccination schedule options available for the different HepB products.

A: The schedule for HepB vaccination depends on the brand in use. Heplisav-B is administered intramuscularly on a 2-dose schedule with doses separated by 1 month (4 weeks). Routine primary vaccination with PreHevbrio, Engerix-B, Recombivax HB, or Twinrix consists of three intramuscular doses administered on a 0-, 1-, and 6-month schedule.
Alternative vaccination schedules for Engerix-B and Recombivax HB (for example, 0, 1, and 4 months or 0, 2, and 4 months) have been demonstrated to elicit dose-specific and final rates of seroprotection similar to those obtained on a 0-, 1-, and 6-month schedule. Increasing the interval between the first 2 doses has little effect on immunogenicity or the final antibody concentration. The third dose confers the maximum level of seroprotection and provides long-term protection.
Recombivax HB may be administered in a 2-dose schedule at 0 and 4–6 months for adolescents age 11 through 15 years using the adult formulation (1.0 mL). Pediarix (GSK) and Vaxelis (MCM) combination vaccines are administered at age 2, 4, and 6 months; they are not used for the birth dose. Twinrix may be administered on an accelerated 4-dose schedule at 0, 7, and 21–30 days, followed by a dose at 12 months.
HepB vaccination of adult (age 20 years and older) hemodialysis patients consists of high-dose (40 µg) Recombivax HB administered on a 0-, 1-, and 6-month schedule or high-dose (2 mL) Engerix-B administered on a 0-, 1-, 2-, and 6-month schedule. Heplisav-B and PreHevbrio have not been studied in patients on hemodialysis.

Q: Can Heplisav-B or PreHevbrio be used to complete a vaccination series started with Engerix-B or Recombivax HB?

A: Yes. However, data are limited on the safety and immunogenicity effects when Heplisav-B or PreHevbrio are interchanged with HepB products from other manufacturers. When feasible, the same manufacturer's vaccines should be used to complete the series. However, vaccination should not be deferred when the manufacturer of the previously administered vaccine is unknown or when the vaccine from the same manufacturer is unavailable.
The 2-dose, 4-week HepB series for adults only applies when both doses in the series consist of Heplisav-B. Series consisting of a combination of 1 dose of Heplisav-B and a vaccine from a different manufacturer should consist of 3 total vaccine doses and should adhere to the 3-dose schedule minimum intervals of 4 weeks between dose 1 and 2, 8 weeks between dose 2 and 3, and 16 weeks between dose 1 and 3. Doses administered at less than the minimum interval should be repeated. However, a series containing 2 doses of Heplisav-B administered at least 4 weeks apart is valid, even if the patient received a single earlier dose from another manufacturer.

Q: Is it safe for a person at risk of hepatitis B to be vaccinated during pregnancy?

A: Yes. Many years of experience with Engerix-B and Recombivax HB brands of HepB vaccines indicate no apparent risk for adverse events to a developing fetus. Current HepB products contain noninfectious hepatitis B surface antigen (HBsAg) and should pose no risk to the fetus. If not vaccinated, a pregnant person may contract an HBV infection during pregnancy, which might result in severe disease for the newborn.
Available human data on Heplisav-B and PreHevbrio administered during pregnancy are insufficient to assess vaccine-associated risks in pregnancy. For this reason, until safety data are available for Heplisav-B or PreHevbrio, providers should continue to vaccinate people needing HepB during pregnancy with either Engerix-B or Recombivax HB. Pregnancy testing prior to vaccination is not recommended.
Mothers who breastfeed their babies and need HepB can be vaccinated. Although data are not available to assess the effects of Heplisav-B and PreHevbrio on breastfed infants or on maternal milk production and excretion, there is no theoretical risk to the infant and vaccination with any HepB product is acceptable.

Q: I'm a nurse who received the HepB series more than 10 years ago and had a positive follow-up titer (at least 10 mIU/mL). At present, my titer is negative (less than 10 mIU/ mL). What should I do now?

A: Do nothing. Data show that vaccine-induced anti-HBs levels might decline over time; however, immune memory (anamnestic anti-HBs response) remains intact following immunization. People with anti-HBs concentrations that decline to less than 10 mIU/mL are still protected against HBV infection. For healthcare professionals with normal immune status who have demonstrated adequate anti-HBs (at least 10 mIU/ mL) following full vaccination, booster doses of vaccine or periodic anti-HBs testing are not recommended.

Q: Who should not receive HepB?

A: A serious allergic reaction to a prior dose of HepB or a vaccine component is a contraindication to further doses of HepB. Engerix-B, Recombivax HB, Twinrix, and Heplisav-B are synthesized in yeast cells into which a plasmid containing the gene for HBsAg has been inserted. People with a severe allergic reaction to yeast should not be vaccinated with vaccines produced in yeast cells. PreHevbrio is produced in mammalian cells and may be used (in the absence of other contraindications) in an adult with a severe allergic reaction to yeast.
As with other vaccines, vaccination of people with moderate or severe acute illness, with or without fever, should be deferred until the illness improves. Vaccination is not contraindicated in people with a history of multiple sclerosis, Guillain-Barré syndrome, or autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis.

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COVID-19 Vaccination Questions

Q: How does CDC define being “up to date” on COVID-19 vaccination?

A: CDC has used the term “fully vaccinated” to refer to people who have completed a primary COVID-19 vaccine series. CDC currently uses the term “up to date” (UTD) to refer to a person who has received all recommended doses in their primary vaccine series, and all booster doses recommended for them, when eligible.
As of May 20, 2022, immunocompromised people age 12 years or older and all people age 50 years or older should receive a second booster dose of either Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine at least 4 months after their first booster dose to be considered up to date.
People age 18 through 49 years who received a Janssen COVID-19 Vaccine (Johnson & Johnson) for both their primary and booster dose may get a second booster dose of an mRNA COVID-19 vaccine, but the second booster dose is not required for these individuals to be considered up to date.

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Q: What are the recommendations for COVID-19 vaccination of children younger than 12 years?

A: On November 2, 2021, ACIP voted to recommend COVID-19 vaccination of all children age 5 through 11 years with two 10 mcg (0.2 mL) doses of the orange cap (dilute before use) formulation of Pfizer-BioNTech COVID-19 Vaccine, administered 21 days apart. On May 18, 2022, ACIP voted to recommend that all children age 5 through 11 years should receive a single booster dose at least 5 months after completion of the primary vaccination series.

On January 4, 2022, CDC recommended that children in this age group with moderate or severe immunocompromise receive an additional primary dose at least 28 days after dose 2. On May 18, 2022, CDC recommended that these children also receive a booster dose at least 3 months after completing their primary series (for a total of 4 doses). 

CDC has summarized the current recommended immunization schedule for all age groups in this print-ready document:

Q: What is the recommended interval between dose 1 and dose 2 of mRNA vaccines for people age 5 years and older and why did it change?

A: CDC has adjusted its recommendations to provide the option of an 8-week interval between doses 1 and 2 of mRNA vaccines for certain people age 5 through 64 years. Large observational studies in other countries have provided evidence that an 8-week interval may result in higher antibody levels and a reduced risk of vaccine-associated myocarditis, which is most likely to occur after dose 2. For this reason, an 8-week interval may be optimal for some people age 5 years through 64 years, especially males age 12 through 39 years who are at the greatest risk of myocarditis after dose 2.
Shorter intervals (3 weeks for Pfizer-BioNTech; 4 weeks for Moderna) protect the recipient more quickly. Therefore, a shorter interval remains the recommended interval for the following groups:

  • All people who are moderately to severely immunocompromised
  • All adults age 65 years and older
  • Others who need rapid protection due to increased concern about community transmission or risk of severe disease

Q: What is the recommended first and second booster dose schedule for recipients of an mRNA COVID-19 vaccine primary series?

A: As of May 18, 2022, ACIP recommends that all people age 5 years or older who completed a primary series of an mRNA COVID-19 vaccine should receive a booster dose of an age-appropriate COVID-19 vaccine (preferably an mRNA vaccine). Among those who are immunocompetent, the interval between the final primary series dose and the booster dose should be at least 5 months. Those who are moderately or severely immunocompromised should receive their first booster dose at least 3 months after the third dose of their primary series.
Among those who receive an mRNA vaccine primary series and who have had a first booster dose, some also should receive a second mRNA booster dose at least 4 months after the first booster. Those who should receive a second booster dose include all age 50 years or older and all age 12 years or older who are moderately or severely immunocompromised.

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Q: What is the recommended booster dose schedule for recipients of the Janssen COVID-19 Vaccine (Johnson & Johnson)?

A: People age 18 years or older who received the single dose of Janssen COVID-19 Vaccine primary series should receive a single COVID-19 booster dose (an mRNA vaccine, unless use of an mRNA vaccine is not feasible) at least 2 months (8 weeks) after the Janssen COVID-19 single primary dose. Those who are moderately or severely immunocompromised and receive a single Janssen primary dose should receive an additional primary dose of mRNA vaccine at least 28 days later, followed by a booster dose at least 2 months (8 weeks) after the additional primary dose. A second booster dose of mRNA vaccine, administered at least 4 months after the first, should be given to Janssen vaccine recipients age 18 years or older who are moderately or severely immunocompromised and to all who are age 50 years or older.
Individuals age 18 through 49 years who have not received an mRNA vaccine because they received Janssen vaccine as both a primary dose and first booster dose also may receive a second booster dose of mRNA vaccine at least 4 months after the first booster dose (for a total of 3 doses).

Q: Should people who have had COVID-19 illness be vaccinated?

A: Yes. Vaccination should be offered to individuals regardless of history of prior SARS-CoV-2 infection. People who are unvaccinated have a higher risk of reinfection than those who are fully vaccinated following natural infection. CDC has summarized the available data on vaccine-induced immunity and disease-induced immunity here:
Viral testing to assess for current SARS-CoV-2 infection or serologic testing to assess for prior infection for the purposes of vaccine decision-making is not recommended. However, as with all vaccines, vaccination should be deferred until after recovery from moderate to severe illness. In addition, to minimize the risk of exposing others to SARS-CoV-2 virus, vaccination of a person diagnosed with COVID-19 generally should be deferred until criteria have been met for individuals with COVID-19 illness to discontinue isolation.
Although waiting to vaccinate after infection is not necessary, people who recently had SARS-CoV-2 infection may consider delaying a primary series dose or their first or second COVID-19 vaccine booster dose by 3 months from symptom onset or positive test (if infection was asymptomatic). According to CDC, increasing the time between infection and vaccination may result in an improved immune response to vaccination. At this time, there is evidence of a low risk of reinfection in the weeks to months following infection. A recipient’s individual risks for severe disease and current COVID-19 conditions in the community should be taken into account when deciding whether to delay vaccination up to 3 months after infection.

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ISSN 2771-8085

About IZ Express

IZ Express is supported in part by Grant No. 1NH23IP922654 from CDC’s National Center for Immunization and Respiratory Diseases. Its contents are solely the responsibility of and do not necessarily represent the official views of CDC.IZ Express DisclaimerISSN 2771-8085

Editorial Information

  • Editor-in-Chief
    Kelly L. Moore, MD, MPH
  • Managing Editor
    John D. Grabenstein, RPh, PhD
  • Associate Editor
    Sharon G. Humiston, MD, MPH
  • Writer/Publication Coordinator
    Taryn Chapman, MS
    Courtnay Londo, MA
  • Style and Copy Editor
    Marian Deegan, JD
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    Laurel H. Wood, MPA
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