Options for HBV Vaccine Non-Responders



Are you a hepatitis B vaccine non-responder? Approximately 5-15% of people who receive the vaccine are considered non-responders. This is especially important for health care workers, families living in households with people that have HBV, and others who may be at increased risk of exposure to HBV.  A vaccine non-responder is someone that does not build up an adequate immune response after receiving two, 3-shot series of the HBV vaccine.  In other words, they complete one series of the HBV vaccine, and follow it with a surface antibody test (HBsAb or Anti-HBs) 4-6 weeks following the last injection of the series.  If the anti-HBs titre is not greater than 10IU/l, than the series is repeated, preferably with an HBV vaccine from a different manufacturer, and the person is once again tested for immunity by testing for adequate anti-HBs. (See previous blog, “Got Hepatitis B? Keeping loved ones safe though HBV vaccination” for details)

Fortunately there are other options for those concerned with being an HBV vaccine non-responder. There is a higher concentration of the HBV vaccine recommended by the CDC that is used for patients undergoing dialysis, and for those that are immune suppressed.  It is a 40µg/ml concentration. If it has been one year or less since you completed the three-shot series of the regular concentration of the vaccine, you can try one intramuscular dose of 1.0 ml of the 40µg HBV vaccine.  If it has been more than one year since your last three shot series of the vaccine, you can repeat the entire three-shot series with the 40µg concentration of the vaccine.  Follow up with an anti-HBs titre test 4 to 6 weeks following the last injection to ensure it is greater than 10 IU/l, and that you have adequate immunity.

If you continue to remain a non-responder, you can try a series of as many as five intra-dermal injections, given every two weeks, using the 40µg concentration of the HBV vaccine.  Dose one consists of 0.10 ml of the 40µg/ml vaccine, followed by the same dose two 2-weeks later.  At that time an anti-HBs titre test would be drawn to check for immunity.  If there was not adequate immunity, a third-intra-dermal dose of the vaccine would be given two weeks later.  Anti-HBs titres would be checked every two weeks and the patient would be given another intra-dermal injection up to a total of 5 intradermal injections of the 40µg concentration of the HBV vaccine. Don’t forget to ensure that your anti-HBs titre is greater than 10IU/l.

Please note that the schedule for the series might vary depending on the study your doctor chooses to follow.  However, it is recommended that the higher concentration (40µg) of the hepatitis B vaccine be used for best results.

50 Responses to Options for HBV Vaccine Non-Responders

  1. My 20 year old daughter is a Phlebotomist. She was told she was a non- responder when she was tested, vaccinated for her first job at a hospital. Her origional vaccinations as a child were done on scedule with no apparent problems. Her family physician referred her to a Hemotologist, who referred her to a Infectious disease Dr, who referred her to. Gasterologist, who only deals with patience with Hepatitis. Who would we contact about information on how to protect her and get more information for non- responders and the new intermuscular vaccine?

    • This blog was written with direct input from our senior medical adviser on the described protocol for HBV vaccine non-responders. I assume that she has gone through two rounds of the vaccine without success and has been tested to be sure she does not have a current or even an occult HBV infection. Did she try the higher dose of the 40µg/ml concentration vaccine? If she continues to be a non-responder, she can try the 40µg/ml concentration of the vaccine for the intra-dermal vaccine. I would take a copy of this blog to your doctor. If he is unsure, he or you can contact the Hepatitis B Foundation at http://hepb.convio.net/site/PageServer?pagename=contactus, or from the contact button at the top of our website at http://www.hepb.org. . Thank you!

  2. Yes she wen’t through the two rounds without success and is testing cleared, with no signs of HBV. I will bring her Dr a copy, she has not heard of any stronger vaccine. Thank you so much for your rapid and helpful response!

  3. I work in healthcare and was glad to read this. I just finished my second series of Hep B vaccinations 6 weeks ago, and had my blood drawn today to check for titers. If I still come back negative, I know I need further work-up and want to know what options I have. Thank you!

  4. Laura M. Greenfield

    I’m also work in healthcare, and I’m glad I found this site! I originally had the 3 doses back in 2005 (3/05-9/05).

    Today I found out that my HepBsAG was negative.

    I looked back in my records and in 11/05 my antibody test showed me at 1420mIU/mL.

    My question is, why/how am I now considered not immune?

    • I think you mean your anti-HBs or HBsAb is negative and not your HBsAg. It looks like you had an anti-HBs test 1-2 months following the last shot of the series and clearly built up and adequate immune response with a titre of 1420! Over time the immune response may wane and the titre may drop below 10, which is considered an adequate response … when checked 1-3 months following the last shot of the series. If you initially generated an adequate response, which you did, then your immune memory will kick in should you be exposed to HBV, thereby once again generating an immune response and protecting you. Hope that makes sense. It’s all about immune memory.

  5. I am a NR with a negative antigen titer for Hep. B. had three series of the vaccine in a timely fashion with the original live (attenuated) virus. That’s three times full series remain NR. Heavily exposed to variety of viral hepatitis patients and have been since I was a kid, now seventy years old.

    Yes, I could go to a higher 40 units but suspect that won’t change my titer. Suspect a gene preventing my conversion to a responder? Yes, I beleive my ancestry came from Eyam, England.

    Why the exposure, a general surgeon and work in County Hospital Micro/lab. Ten years.
    What do you say.

    • Dr. Thomas London, VP of the HBF board and a member of the board of medical and scientific advisors, says that you may be correct that you are a genetic non-responder, but there is no available information on what the gene or genes might be. Nevertheless, Dr. London recommends that you try the intradermal injection route. Specifically, 1.0 ml of the concentrated vaccine for dialysis patients is given with a tuberculin syringe into the skin. Injections are given every 2 weeks with an antibody test done before the next injection. If you do not respond after 6 injections, then you really are a non-responder. And of course you should take all precautions to avoid exposure -,gown and mask whenever you might be exposed to a patient’s blood.

  6. .ano pong gwin k.ngpositve po ako s hepa-b?

    • Ako ng paumanhin.Ko bang ilagay ang iyong tanong sa google translate, ngunit Hindi ako sigurado kung ano ang ikaw ay humihingi.

  7. toothfairy 1968

    Been offered my dream job after 5 years of trying to gain entrance …
    Ambulance technician. I am HepB non responder will this effect my occupational health review?
    Help … I am really panicing . I work in healthcare at the moment as Health care support worker and previously as dental nurse.

    • Have you been tested to confirm that you do not have HBV? If you have HBV you will not generate an immune response to the vaccine. If you know you are not HBV+, have you gone through the process described in the blog: “Options for vaccine non-responders”? The higher dose vaccine will hopefully permit you to generate immunity. However, there is a low percentage of the population that are vaccine non-responders. I do not know the requirements of the job. Perhaps you can sign a waiver for the vaccine?

  8. nice article.. Thanks for sharing

  9. I’m one of the non responder after getting 2 sets heb B of vaccination. I am considering to get the double dose concentration but I want to know what is the success rate after getting the 40 mcg vaccine that non responder will become immune?

    • I’m afraid I don’t have specific study data. If you feel especially at risk or need to show a generated titre for work or school, then I would certainly consider it. Keep in mind you can also avoid transmission of HBV by taking basic precautions, which includes avoiding direct contact with any blood or body fluid by maintaining a barrier. For example, keep any open cuts covered, and practice safe sex with a latex condom. Always avoid sharing personal items such as razors, toothbrushes, clippers, earrings, piercings, or anything that could have trace amounts of blood on it. Be sure to clean all spilled blood or body fluids with a fresh diluted bleach solution. Take care with piercings and tattoos and be sure all items are single use. Never share drug paraphernalia. These are basic precautions that should be taken to prevent the transmission of other blood borne pathogens for which there are no vaccines available.

  10. Hi, I’ve just found discovered I am a non-responder. I am leaving for a 2 month trip of lifetime to Africa in ten days – my doctor has recommended HepB immunisation before I go. I can delay the start of this trip by a couple of weeks as a worst case scenario, but I would prefer to leave as soon as possible. What are my options?

    • A person is considered a nonresponder if you have gone through 2 complete vaccination series. Here are a couple of options: Note the higher concentration dose of the virus noted in the blog “Options for HBV Vaccine Non-Responders” . There is an accelerated travel vaccine schedule given at day 0, Day 7, Day 21 and month 12. Talk to your doctor about trying the first 3 shots of this series with the higher dose concentration. If you do not generate immunity, then talk to your doctor about getting a shot of HBIG right before you leave for your trip.

  11. Had needle-pricked with hepaB positive patient and i just had my hepaB vaccine after 3weeks.Is it effective?i’m very worried maybe i got infected..

    • Did you receive all 3 shots of the series? If you are in health care, they often run an anti-HBs titre 1-2 months following the last shot of the HBV vaccine series to ensure the person has generated an adequate titre and is protected. You can ask and see if you had this test. If you had it and know you are protected, then you are all set. If you are unsure, or did not complete the series, then I would get a booster shot of the vaccine. Regardless, I would still ask your doctor for a hepatitis B panel just to be sure. Be sure to wait 4-6 weeks following your exposure.

  12. Respected Sir,
    I am working as a nurse in theatre they checked titre for all staff all of them having above 10iu but in different ranges,for me 200 some ofthem above1000iu,others with 54,110etc sir most of them didn’t take booster dose can u clear my doubt when we should repeat another dose if range is below…..please reply it early as possible
    thanku verymuch.

    • Since all of your staff have anti-HBs titres above 10 IU/mL, this means they have generated adequate immunity and are protected against getting HBV for at least 25 years, which is the current length of on-going studies. Often titres will wane, but that doesn’t mean someone isn’t protected. If they were exposed, they would mount a fight against an infection. THis is assuming they generated immunity as a result of the vaccine series, since there are non-responders to all vaccines. Typically people do not have their titres checked 1-2 months following the vaccine series. It’s not required, but if you are at-risk, it’s certainly worthwhile. People may worry years later and then have their titres checked. At that point, the titres could wane and you wouldn’t know if they initially generated adequate immunity or if the titres just waned. If the titres waned and they did not show adequate immunity (<10IU/mL) then, they would need a booster and they could have titre's checked 1-2 months following the booster. The variations of titres merely reflects each person's unique immune response to the vaccine series. Hope that clarifies it a bit.

  13. my 7 year old’s titres came back low for hep B and the doctor recommended starting the series again. He was given his first dose yesterday. Are more doses necessary? I am a bit surprised that his titres were tested for hep B in the fist place as he is a healthy child and also we ( his parents) have been vaccinated. Please advise if only the first dose is enough. Thanks!

    • According to the CDC, a booster dose should be sufficient. However, should you choose to confirm immunity, you can have him get his titres checked 1-2 months following the booster shot.

  14. Thanks for the info!

  15. Ive been diagnosed with hepa B but my mother told me id been vaccinated completely with booster and yet my hbsag becomes reactive, anti hbs non reactive, hbe eag 13.33 reactive and hbe ag non reactive… what does this means

    • You currently have a hepatitis B infection. Most likely you were already infected before you were vaccinated. The vaccine is not effective if a person is already infected with HBV. Please talk to your doctor to learn more about your HBV and liver health.

  16. I had one set of the 3 vaccine shot and came back non-reactive . dose that mean that I have hep-b

    • You mean you did not generate adequate immunity? – anti-HBs less than 10 IU/mL? Some people are non-responders to the HBV vaccine (this is considered after 2 failed attempts to generate immunity after 2 complete HBV vaccine series), but if you believe you may have hepatitis B, then ask your doctor to run a hepatitis B panel to see if you have an HBV infection.

  17. If some one is HBSAg positive, but HBeAg, HBcAg, HBeAb, HBcAb are both negative, please what does that mean?

    • Little confusion here with your question and test results. Usually when someone is HBeAg neg/pos the other HBeAb is the opposite, unless they are in the middle of seroconversion. This is certainly possible, so you would want to retest in a few months to see if you are successful in seroconverting. HBcAg is only positive on biopsy rather than serology, so that would be normal. Most people that test HBsAg positive are nearly always also HBcAb positive. Once again, retest to be sure there is no false positive or to confirm results. ultimately the answer answer here is – rested with a reliable lab and liver specialist

  18. My fiancée was diagnosed to be hep B positive. I did my test and was declared negative. I have taken the first vaccine shot and am expecting to take the second shot 3 days before we start having unprotected sex.while waiting to take the last shot 6 months from now. Will I be protected by these first two shots

    • After the 2nd shot of the HBV vaccine you are UP TO 80% protected against HBV. There are a few factors involved, but everyone is different and I cannot give you any guarantees. If you like you can get a titer test 1 month following this 2nd vaccine or following the last shot of the series to confirm immunity. I would encourage your fiancé to be patient.

  19. I was told that I’m a healthy he b carrier, can I work as a medical assistance in a hospital?

    • That will depend on what country you live. If you live in the U.S. this should not be a problem. HBV is covered under the Americans with Disabilities Act and the CDC revised guidelines for healthcare students and workers. Let us know if you have a problem. If you live in another country, it’s completely dependent on their policies.

  20. I seem to a non-responder to HBV and other vaccines. I’ve had infections as a child that later tested negative anti-body titers with subsequent vaccinations that years later also show negative anti-body titers. Rubella, Varicella, Mumps….I was vaccinated with HBV in 2003 with a postive ab response and negative ag response (can’t get measurement from hospital) but just had titer checks that show non-reactive for ab or ag. I am an ER nurse and am not thrilled about the prospect of going through a series of a potential 6 vaccinations with HBV only to continue to be a non-resonder since I have a poor track record with vaccines. I’ve obviously been exposed through the years to many of these infections several times due to my work and raising 2 children. Can I make a decent supposition that I have “immune memory” and with proper protective equipment and following protocol continue in a safe manner as an ER nurse without more vaccinations? Or could this kind of history indicate “genetic non-responder” Currently hospitals are requiring several vaccines for employment and termination if not completed unless there are medical contraindications. Can someone give me a well versed opinion? Thank You

    • A person is considered a non responder after 2 complete series of the vaccine followed by an inadequate titer drawn 1-2 months following the last shot of the series. I know you seem to be a non-responder to some vaccines, but unless you had a titer to confirm your immunity 1-2 months following the last shot of the vaccine series, then I would get a booster shot and test 1 month following the booster with an anti-HBs titer test. If you generate immunity then you do not need to repeat the vaccine series even if your titers wane over time. If you truly are a non-responder then you could try vaccinating with a higher concentration of the vaccine. Most hospitals are requesting proof of titers. Regardless, I would think following proper infection control practices would still be adequate since there are not vaccines for all blood borne pathogens such as HIV and HCV. With any luck you can generate immunity, but if not strict following of infection control practices should be adequate. I would not think being a non responder should keep you from working.

  21. Hi I would appreciate if you could answer my question. I am from England and I received the full hep b vaccinations which I received the third vaccination in December 2006. As worked at a hospital at this time in late January 2007 I was checked to see if I responded to the vaccinations and the reading from that blood test was more than 100. I recently requested to be checked to see if I still had immunity from the vaccine and I have been told that I have no immunity. I am upset and concerned by this as it has only been 8 years since I had the vaccination. I thought the protection lasted much longer. I am worried tha

    have come in contact with the virus and not have been protected.

    have come into contt with the virus and not been protected

    I am concerned that


    may have come in contact with the virus and not been protected. Would I need to

    immune and still protected from the vaccine. I was informed that I am not immune. I am concerned that after 8 years I am no longer protected by the vaccination. My fear is that I could have been in contact with the virus and not been protected. I was tested for the virus in 2011 during pregnancy which was negative at that time

    rstill protected from the vaccine. I was informed that I am not immune. I am cocerned by this as when I received the vaccine I was responsive to it but now afte

    • You are protected. If you were to be exposed to HBV, you would generate immunity. It is not unusual for the anti-HBs titers to wane over time. The difference is that many do not have their titers checked after they are vaccinated so they don’t know if they ever generated immunity. That is not the case with you since you know you generated immunity since you had a previous titer of 100+. On going studies show that immunity is good for greater than 25 years assuming immunity was generated as a result of the 3 shot vaccine series.

  22. Hi..

    Recently i have taken blood test
    Anti HBS Shows 4.72IU/L … can anyone help me on that value?
    does it mean that i’m affected by Hepatitis B?

    • The anti-hsb is the antibody to hepatitis B. If you want to be tested for hepatitis B, you want to ask that your HBsAg (surface antigen) is tested. A person is considered immune to hepatitis B if there anti-hbs titer is greater than 10 IU/mL. Were you vaccinated or do you believe you were exposed? if you ask the doctor to run a hepatitis B panel, it tests for 3 things: HBsAg, HBcAb, HBsAb. When read together it tells you if you have a current infection, if you resolved a past HBV infection or if you have immunity to HBV whether it is from a past infection or through vaccination.

  23. Please help me interpret these results:
    HBsAg Screen Positive
    Hep A Ab, Total Negative
    Hep B core Ab, Tot Negative
    Hep B Surface Ab, Qual Reactive

    *by the way I was vaccinated with the Hep B series vaccine as a child.

    • Your results are a bit unusual. Have you also been tested for hepatitis C? Are you being tested as a result of elevated ALT/AST and/or other liver function tests? Please talk to your doctor. Repeat testing and see if the results are the same. Your test indicates that you are positive for hepatitis B, but your core antibody and surface antibody are negative, which is unusual. If you continue to test HBsAg positive, but do not have another infection or problem identified by your doctor and more blood work, then be sure to see a liver specialist to learn more.

      • I was tested for Hep C and it came out negative..I had elevated ALT/AST but when I got retested they were back to normal. I’m very confused and worried. I did have more blood work done and I’m now just waiting for the results.

        • Try not to worry Kay. I think the blood work will reveal more of what is going on. If you continue to have confusion, please be sure you are seen by a hepatologist or GI doctor with experience treating viral hepatitis.

  24. Please help me interpret these results.
    HepBsAg negative
    HepBsAb positive titre 835
    HepBcAb positive

    • You have immunity to hepatitis B and it looks like you got that because you had resolved a previous hepatitis B infection.

  25. Hi my partner is hep b positive, I have had the 3 vaccines and I am none responsive I have had 2 more of the next 3 my last vaccine due in 5 months what are the chances this 2nd treatment will make me immune??

    • Have you been tested to be sure you are not currently HBV positive? Often when a person is a non responder, it is because the have or had an infection. Is the 2nd vaccine series a made by a different manufacturer than the first series? This is recommended. Another option is to ask for a vaccine of a higher concentration, especially since your partner is HBV positive, if you do in fact not respond. I cannot give you any specific statistics, though there is a percentage of the population that does not respond to the vaccine for whatever reason. I would also try the higher concentration if this series does not work. Also consider Hepislav, which will hopefully soon be on the market. Sci-B-Vac is also a good vaccine, but I don’t think it’s available in the U.S.

  26. I have been employed as a medical secretary in a hospital for 15 years. Yesterday when I had my TB test, I was on my way out the door when the secretary handed the nurse a printout of some lab work from 2012, the same year I was diagnosed with breast cancer and went through surgery, chemo, and radiation. He showed me where it said I was nonresponsive to the vaccines I got upon employment. But, he said, since my job & lifestyle doesn’t involve being in contact with blood or blood products, I haven’t traveled out of the country in over 10 years, and I don’t work closely with patients in countries that have a high level of plague and disease, he would consider me low risk and he left it up to me whether I wanted to try a booster. I don’t want a vaccine I don’t need, but I am wondering how safe it is to not have an immunity to Hep B. Your observation and input would be welcome. Thank you.

    • I’m not quite sure what to tell you. it certainly does not sound like you are at risk for HBV with your job as a medical secretary. HBV is not casually transmitted or contagious like TB. Plus the anti-HBs titer test that was likely run in 2012 may not be an accurate reflection of your immunity. I’m not sure when you were vaccinated, but it’s not uncommon for the titer to wane with time. Had you been tested 1-2 months following the last shot of the series, you may have found that you generated adequate immunity. Had you proof of immunity, there would be no question. You would not be to get a booster. However, it sounds like you didn’t. If its a concern for you, you could have a booster shot, followed by an anti-HBs titer test 1-2 months following. If you generate adequate immunity then you are protected despite whether or not your titers wane with time. Let me know if you have other questions.

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