Adults have cross-reactive antibodies to A/California/04/2009 (H1N1)

22 May 2009

hemagglutinationDoes previous exposure to influenza H1N1 viruses, either by infection or vaccination, provide any protection against infection with the new H1N1 influenza virus strains? The answer to this question might provide insight as to why over 60% of confirmed cases of influenza caused by the swine-like H1N1 viruses in the US are in 5- to 24-year-olds, as reported at a CDC press conference.

To answer this question, CDC has analyzed serum specimens that were collected during previous vaccine studies. These sera were collected from children and adults before and after they received influenza vaccine in the 2005-06, 2006-07, 2007-08, or 2008-09 influenza seasons. Virus neutralization and hemagglutination-inhibition assays were done to determine whether these sera contain antibodies that cross-react with the new H1N1 strain. The authors of the study used the A/California/04/2009 as a representative of the new H1N1 virus isolates.

The results show that previous immunization of children (age 6 months to 9 years, total of 79 specimens) with either seasonal trivalent inactivated vaccine or infectious, attenuated influenza vaccine of the previous four years did not induce cross-reactive antibody to the new influenza A H1N1 strain. Previous immunization did induce a low cross-reactive antibody response to A/California/04/2009 in adults. Among 18-64 year olds, there was a twofold increase in cross reactivity antibody to the virus, compared with a 12-19 fold increase in antibody titers against the seasonal strains. There was no increase in cross reactive antibodies in adults over 60 years of age. These data indicate that immunization with seasonal influenza vaccines containing previous H1N1 strains (years 2005-2009) is not likely to confer protection against infection with the new H1N1 strains.

An important question is whether the sera obtained before administration of vaccine contain cross-reactive antibody titers against A/California/04/2009. Such analyses would indicate whether natural infection with H1N1 strains confers some protection agains the new isolates. There were no pre-vaccination cross-reactive antibodies to A/California/04/2009 in sera of any of the 79 children of ages 6 months to 9 years. However, 6% of adults 18-40 years old, 9% of adults 18-64 years old, and 33% of adults over 60 years of age had pre-vaccination neutralizing antibody titers to A/California/04/2009 greater than or equal to 160. These antibodies were likely acquired by infection with an H1N1 virus that is antigenically more similar to the A/California/04/2009 than other seasonal H1N1 strains. Whether such antibodies would confer protection against infection is unknown, but they could reduce the severity of disease symptoms.

I suspect that not all readers of virology blog are familiar with the microneutralization and hemagglutination-inhibition assays used in this study. In a separate post, I will explain how the assays work, and the significance of the test results.

J Katz, PhD, K Hancock, PhD, V Veguilla, MPH, W Zhong, PhD, XH Lu, MD, H Sun, MD, E Butler, MPH, L Dong, MD, PhD, F Liu, MD, PhD, ZN Li, MD, PhD, J DeVos, MPH, P Gargiullo, PhD, N Cox, PhD (2009). Serum Cross-Reactive Antibody Response to a Novel Influenza A (H1N1) Virus After Vaccination with Seasonal Influenza Vaccine Morbid. Mortal. Weekly Rep., 58 (19), 521-524

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  • Matt Dubuque

    One thought comes to mind. If I was exposed to an H1N1 virus from some rude person sneezing near me many years ago, I would have been exposed to a quasispecies of H1N1, with a myriad of viral particles across a spectrum of different genotypes.

    My cursory understanding, which may be mistaken, leads me to believe that if I was vaccinated against a particular H1N1 strain, I would have been exposed to a smaller range of viral diversity.

  • http://www.virology.ws profvrr

    You are likely correct in your scenario. It is likely that the
    spectrum of viruses produced in an egg is much more restricted than
    the viruses produced in someone's respiratory tract. New sequencing
    technologies are making it possible to actually find out.

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  • Jason R

    “over 60% of confirmed cases of influenza caused by the swine-like H1N1 viruses in the US are in 5- to 24-year-olds, as reported at a CDC “

    I'm going to suggest that 60% is inaccurate. We are 55, 57 and 76. We all got it easily and had 3 variations for a month each. My guess is that every one has an equal probability of contracting it that comes in contact with it.
    My question is: Can we make antibodies to combat a Frankenstein virus? I had a severe case. I contracted it via my steering wheel that my mechanic touched weeks after he contracted it. It is very contageous. Can I get tested for these antibodies?

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  • Cosmoskitten

    “Among 18-64 year olds, there was a twofold increase in cross reactivity antibody to the virus, compared with a 12-19 fold increase in antibody titers against the seasonal strains.”

    I wonder that this twofold increase means.

    If you have had regular flu vaccinations in the past, are you _slightly_ better of with regards to swineflu 2009?

  • http://www.virology.ws profvrr

    The twofold increase is probably not helpful in terms of protection.
    What would help is if you received the 1976 swine flu vaccine – those
    individuals have cross protective antibodies against the pandemic H1N1
    strain.

  • troy

    So the question is if there is an antibody test for checking if a person has already had exposure to the new strain of H1N1 ?

    There is one available for pigs, horses, and other livestock from IDEXX.com

    but none for humans ?

    How do they check if the vaccines are working or if people already have immunity ?

    If someone already has immunity, then the available vaccine supply would be better
    served to those who need it.

    What is the chance that people already have immunity ?

  • troy

    check out http://www.idexx.com
    you can find out if a horse or pig has had the h1n1 new strain
    but not humans. i would think that testing for antibodies BEFORE
    vacccination would serve the population and supply of vacc's better

  • http://www.freedomcrowsnest.org/ Jason R

    I'm 55 and had a case of H1N1 pretty bad in June. Nearly half of our children are out of school with “flu like symptoms”. Half of the check out people at the grocery store have it. As I've heard that people that got a mild case, got it over again, up to 3 times this summer, I might actually be immune now. It could be that one needs to have a severe case to make all the antibodies necessary to fight this weapons grade, man made virus off. It's my hope that this virus goes the way of the 1976 weapons grade virus and dies off.

  • Mary

    How do we know if we are “immune” to this species of H1N1? If we get a mild case – muscle aches, sore throat, fatigue etc. – can we expect to be protected from a more serious version in the future??

  • http://www.virology.ws profvrr

    The only way to know if you have had influenza is to have a clinical specimen (e.g. nose swab) examined for the presence of H1N1 influenza virus. Clinical symptoms are not enough to confirm that you have been infected with the virus. If you have had a laboratory confirmed infection with H1N1 virus, then you are likely protected for the immediate future – a few years, until the virus changes.

  • Jason R

    Doesn't look like we have anything definitive yet, Mary. I've had it bad in June and been around a lot of sick people at the grocery store lately and I haven't contracted it again. Maybe a good sign.

  • http://www.virology.ws profvrr

    There aren't any rapid tests for antibodies to H1N1 influenza that could be performed in a doctor's office. In any case, it's not practical to test everyone for antibodies before administering the vaccine – that would be a logistical nightmare. There are far fewer livestock animals than humans, hence they can be readily tested.

  • Jason R

    That's good news. I was tested but the lab didn't read the CDCs instructions and ran rapid tests. You can guess the out come. False Neg. I have no doubt it was H1N1. It literally couldn't have been anything else. The symptoms are too different from seasonal flu.

  • Tamara

    Members of three families, including mine, all came down with seasonal flu-like symptoms this summer within a couple of days after one of them was on a flight from New York; we were all exposed to each other at a 4H meeting. Severity of symptoms ranged from mild to incapacitating. At the time, we joked about it being the swine flu, so now we are wondering if we have immunity and can skip the immunizations, since supplies are limited and should go to those in greatest need. I was just reminded of it this evening when the blood bank called asking me to make an appointment for a donation; afterward, I wondered if there is a blood test for antibodies, and if a blood donation could help confer resistance (I realize that blood donations end up mixed, so the effect on any individual donor would be minimal).

  • http://www.virology.ws profvrr

    Unfortunately there isn't a blood test for antibodies that is widely used for clinical purposes. There are assays for such antibodies (see this post at virology blog for an example: http://bit.ly/3seRTe) but they are only used for research purposes. You are correct that the antibodies would be diluted in the blood supply; but usually you should not give blood if you have had a recent infection (they usually ask you before donating).

  • Sasha Kay

    I believe I contracted H1N1 in August and was treated in the hospital. Can I be tested for H1N1 antibodies?

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  • Mindy

    Very interesting read. I have wondered about testing for antibodies since I am pregnant and my daughter had classic H1N1 symptoms weeks ago and I never got sick. I am 33 years old (born in 1976) and my mother was vaccinated against the Swine Flu of the time (1976) while pregnant with me and I was breastfeed.

  • http://www.virology.ws profvrr

    Given that history you should not have antibodies that would protect
    you against 2009 H1N1 – your mother might have passed antibodies to
    you in her milk but those would have been long gone.

  • maximusmarkermus

    Don't you wish that people would understand that by referring to a specific Influensa A virus with a Taxon ID # 641501, A/California/04/2009(H1N1) : simply as H1N1 are misleading ,there are many, many H1N1 influensa A -virus out there

  • Arrgy

    I don't think any one is confused as to which strain we're talking about but i do wish they'd drop the “swine flu” label. Maybe, 2009 weapons grade flu or Rumsfelds plague…

  • Neil M

    There are close to 170 million cattle, pigs, and horses in the United States. Or a little over half (55%) of the human population (and 65% of the insured population). On that basis the logistics aren't much different. Now the fact that livestock are usually numbered and kept in pen might help, but I'm still not convinced it's as nightmare-ish in complexity as you suggest. Given the scarcity of the vaccine, it ought to be relatively simple to test those waiting for it be available while they're waiting and get those testing positive out of the line (just take the test sample when they're in for the seasonal flu shot). Just one more thing for the doctor's office to put in the file.

    There's no need to enforce this or report on it at a national level, the would be much more a logistical nightmare.

  • http://www.virology.ws profvrr

    Cattle, pigs and horses obey and don't have other things to do. I've
    had email here from parents who say its' tough to bring their kids in
    for a booster shot. I agree that it might work for some but perhaps
    not enough to make it effective. But I envision some day the doc will
    be able to hold a scanner to your arm and tell you exactly which
    pathogens and antibodies you harbor. Hope I'm around for that.

  • Neil M

    There are close to 170 million cattle, pigs, and horses in the United States. Or a little over half (55%) of the human population (and 65% of the insured population). On that basis the logistics aren't much different. Now the fact that livestock are usually numbered and kept in pen might help, but I'm still not convinced it's as nightmare-ish in complexity as you suggest. Given the scarcity of the vaccine, it ought to be relatively simple to test those waiting for it be available while they're waiting and get those testing positive out of the line (just take the test sample when they're in for the seasonal flu shot). Just one more thing for the doctor's office to put in the file.

    There's no need to enforce this or report on it at a national level, the would be much more a logistical nightmare.

  • http://www.virology.ws profvrr

    Cattle, pigs and horses obey and don't have other things to do. I've
    had email here from parents who say its' tough to bring their kids in
    for a booster shot. I agree that it might work for some but perhaps
    not enough to make it effective. But I envision some day the doc will
    be able to hold a scanner to your arm and tell you exactly which
    pathogens and antibodies you harbor. Hope I'm around for that.