Is it true that Hep B vaccine breakthroughs, when someone has been successfully vaccinated yet becomes infected, are very rare and only occur with certain gene mutations?

I remember reading that or hearing it somewhere but wasn’t sure about the validity of it?

Hi @Anon2023 ,

This is largely true. Vaccine breakthrough infections can occur, but they are remarkably rare. They usually occur due to a few specific mutations in the HBV S protein (abbreviated as HBs or HBsAg). However, those mutations usually weaken the virus (called “reduced fitness” in virology terms), so they don’t spread very well from one person to another.

In short, this is very rare, but can happen.

John Tavis.


Hi @john.tavis thank you for your insight! So can vaccine breakthrough infections only happen with mutations? Meaning, if there is no mutation in the HBV S protein and someone is adequately vaccinated, is a breakthrough still possible?

I believe it’s still possible to get infected even with the unmutated HBV if the immunity against the vaccine declines, either due to disease, some medical treatment or simply aging.

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Hi @Ace thanks for the input! Yes, I’ve heard that immunity can decline overtime - but I do wonder if, with full immunity, vaccine breakthrough can occur even with an unmutated virus.

Also, do you know how common it is for immunity against the vaccine to decline due to disease, medical treatment, aging, etc. and if it does decline, if one would be able to regain immunity from a booster even if they had those aforementioned conditions?

This is correct, but it is not usually considered “breakthrough” in the normal virology context. This is more usually considered to be waning immunity.

To also answer @Anon2023’s comment: Viral growth in the presence of full vaccine efficacy for unmutated HBV is negligible and clinically irrelevant. Immunity can and usually does decline for all the reasons you list, particularly age. If your immune system is not damaged at a fundamental level by something like an uncontrolled HIV infection, booster shots normally work even in the aged, although not as well as in younger people.



Hi @john.tavis that’s really good to know, thank you. I suppose I have somewhat of a concern as I’m negative to Hep B but my partner is positive (he’s an inactive carrier) so I do worry about a long term relationship w/ him bc, even though I have immunity now, what if several years down the line as I start to age, my immunity declines and I’m then unable to regain immunity due to older age (I’m 28 now and I know my body won’t be the same 10, 20, etc years down the line). Or, what if I get some other disease (for example my mom has Rheumatoid Arthritis and I read sometimes it can be genetic) so what if I end up developing that and that messes with my immunity against the virus and am unable to regain immunity due to that disease, etc. lol a lot of what ifs, it’s admittedly nerve wrecking to think about

It is good to be concerned about these things because they are possibilities that would have a major impact on your life! The best thing to do is have your doctor test your anti-HBs antibody titers every 5 years or so, and get a booster if they start dropping to near the cutoff considered to indicate adequate protection (10 mIU/ml if I remember correctly, but be sure to ask your doctor).

Good luck!



@john.tavis thank you for your input! Yes, it is indeed 10 mIU/ml. Trying to be optimistic that I’ll maintain immunity throughout the years and be able to successfully regain it as it naturally starts to decrease due to age, or God forbid, any other medical issue I may develop. And, maybe this is dumb thinking on my part, but he is an inactive carrier with an undetectable viral load, so I always assume that if, in an absolute worse case scenario, one of these days I find I cannot regain immunity, I imagine the likelihood of him even passing it onto me with no immunity would be quite slim, albeit possible. I read several stories of couples being together for years & one of them didn’t even know they were positive and never passed it on to their partner despite the partner not being vaccinated. So I suppose I’ll just try to think positively. Moreover, as science advances I’m hopeful that vaccines will either become more effective in successfully vaccinating people, or, in an even better scenario, he’d loose his positive status, which I understand is very rare, but you never know.


The effect of HBV vaccine not only stimulates B cell which produces anti HBs but can also stimulate T cell lymphocytes especially CD4/CD8 which is the cellular immune respond and can protect the virus if there is waning humoral immunity occur as the time pass.

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Hi @chul_chan thanks for your reply! I’ll admit, I’m a bit confused by what this means lol. Any way you can dumb it down for me? :sweat_smile:

Hi @Anon2023,

@chul_chan is describing different bits of the immune system that get stimulated on vaccination.

One of them is an antibody response, which is what is detected with the anti-HBs test. Antibodies are released into the blood and basically neutralise the virus that is floating around. This stops any infection from happening.

The other one is what is called a humoural response, which is not tested by any commercial test. This is the arm of the immune system that recognises and then kills infected cells.

Hope this clears things up.

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Thank you! I certainly needed that explained to me in layman terms, this helped lol

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