Do women need the same amount of influenza vaccine as men?

28 October 2009

Do Women Need Such Big Flu Shots?” suggests that we would have more doses of influenza 2009 H1N1 vaccine if we accounted for the biological differences between men and women. The idea is that women generate a stronger antibody response than men, and therefore require less vaccine. Does this idea have scientific support?

The opinion is based in part on a study carried out in 2004-05, in which adults were immunized with full (15 micrograms) or half-doses of trivalent inactivated influenza vaccine. This vaccine, made by Aventis Pasteur, contains influenza H3N2, H1N1, and B strains. Serum samples obtained before immunization and 21 days later were assayed for antibody response to each strain of influenza by hemagglutination-inhibtion. I’ve taken the data on geometric mean serum HI titers according to age, sex, and dose and plotted them on a graph:

GMT_HA

Based on the results the authors conclude that “Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage.” But are these immune responses protective?

HI titers of 1:40 or more (which would be reported as 40 or higher in the graph) are believed to indicate levels of antibody that would protect against infection with influenza virus. By this criteria, the full and half dose of vaccine would provide protection agains the influenza H3N2 and B viruses in both men and women. The results confirm that females respond more strongly to the same dose of vaccine than men. But look at the results with the H1N1 strain – in all subjects, no matter the dose of vaccine or gender, the antibody response would not be sufficient to protect against infection. Furthermore, the response is only slightly better than in women.

I interpret these observations to mean that the antibody response to inactivated influenza virus vaccine is not universally more robust in women compared with men – it appears to depend on the virus strain. Clearly clinical studies are required to address this question. Even after spending millions of dollars to decide whether to give women less influenza vaccine, a new strain of influenza virus might come along that induces no better antibody response in women than in men.

My conclusion is that it would not be possible to determine conclusively that women could receive half the amount of inactivated influenza virus vaccine as men. I would rather spend money on developing new ways to produce as much influenza vaccine as needed as quickly as possible – such as by making virus-like particles in plants.

Engler RJ, Nelson MR, Klote MM, VanRaden MJ, Huang CY, Cox NJ, Klimov A, Keitel WA, Nichol KL, Carr WW, Treanor JJ, & Walter Reed Health Care System Influenza Vaccine Consortium (2008). Half- vs full-dose trivalent inactivated influenza vaccine (2004-2005): age, dose, and sex effects on immune responses. Archives of internal medicine, 168 (22), 2405-14 PMID: 19064822

  • http://twitter.com/pjie2 pjie2

    It's startling to me that the H1N1 titres weren't protective in any of the groups. Is that usual, or was it one particular dud batch of vaccine?

  • http://www.virology.ws profvrr

    I also found it curious – and was discussing it this evening with my colleagues here. Bad batch of vaccine, bad HI assay – could be a number of explanations. I'm looking into it further.

  • David

    Finally – I've found the smoking gun on why I get sick more often than my wife. Seriously – can we also assume female's have a stronger immune response due to natural infection across several pathogens?

    David

  • http://www.virology.ws profvrr

    I would not assume that the gender effect applies to all infectious diseases, but there is some evidence that it is observed with a number of different vaccines. Certainly deserves more investigation, especially with respect to the mechanism.

  • gsgs

    I redid the graph here:
    http://magictour.free.fr/panflu/vaxmf.jpg
    so to make it more instructive (IMO)

    > women generate a stronger antibody response than men

    > Half-dose … effective

    I don't think there is some magic 1:40 barrier, at which protection increases
    overproportional.

    > In interpret these observations to mean that the antibody response to inactivated
    > influenza virus vaccine is not universally more robust in women compared with men

    not universally, at usual, no surprise.
    But : “on average”, “there is evidence”, “may” , “could”,

    > My conclusion is that it would not be possible to determine conclusively that women
    > could receive half the amount of inactivated influenza virus vaccine as men.

    would,possible,conclusively,could,
    There is an optimal dose which can be calculated from these data and
    we should use it. Depending on age,gender,weight,…
    The more data, the better.

    > a new strain of influenza virus might come along

    ahh, yes. But it would likely behave similar. And then, it might not (so soon).

    > I would rather spend money on developing new ways to produce as much
    > influenza vaccine as needed as quickly as possible

    spend on both, of course, but how much ? ~$5B spent in the 2005 budget
    on the vax-thing by USA.

    the graph i.e. shows that half-doses are good. Why don't they give half doses
    now, when there is shortage ?

    from the picture I would estimate that women should get 70%-80% of the vax that
    men get.
    You must decide independently whether women should be protected preferrable
    (contact with children…) – that would increase the amount again.
    Not so big difference between the 18-49 and 50-64 groups.

    Why is it, that women have a stronger response ?
    Do they also respond stronger to real infection ?
    But obviously they are not less likely to catch it. Without that
    stronger response maybe(30%) they would get more(120%) flu
    than men (because of exposure to children or )

  • http://www.virology.ws profvrr

    Protection against infection is considered to be conferred by HI titers of 1:40 or greater – it isn't a 'magic barrier' but a number derived from empirical results. This issue has been discussed previously here. The fact that the H1N1 strain does not induce protective responses in men or women means that there are strain specific differences. Hence one cannot simply give women half the dose every year without considering the strain. Why do you think a new strain would behave similarly? It could just as well generate a sub-optimal response in women when a half dose is given – do you want to take that chance? Yearly clinical studies would be required for which there is no time. Spend the money on a better vaccine.

  • gsgs

    > The fact that the H1N1 strain does not induce protective responses in men or women
    > means that there are strain specific differences.

    current predictions for mexflu are good, AFAIK

    > Hence one cannot simply give women half the dose every year without considering the strain.

    one can, but is it reasonable ? Use all data … in absence of other data that graph
    suggests ~70%-80% (not 50%)

    > Why do you think a new strain would behave similarly?

    history

    > It could just as well generate a sub-optimal response in women when a half dose is given –

    could happen, but IMO not just as well

    > do you want to take that chance?

    we always take chances. Do you want to take the chance for more side effects from
    full doses which aren't really necessary ? Do you want to take the chance from giving
    men “only” the amount that women get despite evidence for reduced reaction ?

    > Yearly clinical studies would be required for which there is no time. Spend the money on a better vaccine.

    no time for that either. Except the decision whether to add adjuvants or not

  • http://twitter.com/maryodom Mary Odom

    Hi–
    I just thought I'd add that women often have stronger immune responses than men, and not just humans. A result of this is that female mice are used to make monoclonal antibodies, and other reagents and assays requiring an immune response are almost always done with female animals (rabbits, rats…). Human females are several times more likely to develop autoimmune disorders than human males– the actual amount of difference depends on the particular disorder– SLE (Lupus) especially and MS come to mind as good examples, although some disorders don't show a big gender bias. You can find more info on this in the literature. Offhand I'm guessing it might have something to do with levels of steroid hormones (anti-inflammatory) and their balance with inflammatory cytokines, interleukins, etc.

    Regarding dosing men and women differently for vaccines, please remember that the data are the mean values for individuals describing themselves as male or female– in real life the hormones and potentially other factors responsible for the response differences are on a continuum in the population.

    The discussions here are always interesting– thanks!

  • http://twitter.com/maryodom Mary Odom

    I probably spoke (wrote!) too soon– I know people use male and female mice for making monoclonals. In the lab where I worked we kind of standardized on female for better response, but I don't know of any real data proving that. –Mary [foot in mouth]

  • u2star

    I am interested in getting a titer done before I decide to get the h1n1 vaccine. My doctor will submit sample only id I find a lab myself that will do it. Can anyone help me with this pleas?!!!

  • crapface McGee

    u suck!!!!!!!! i had swine flu and im fine!!!!!!!

  • crapface McGee

    u suck!!!!!!!! i had swine flu and im fine!!!!!!!

  • StereoID

    The fact that women are stronger when it comes to resisting any kind of disease is an old proven fact. I don't know why you are asking such a simple question. Although socially speaking, women are seen as being weak, the truth is that their metabolism is much stronge than what men are “equipped” with.

  • OneChanceOneLife

    Actually, some current medical studies have proven that men are starting to disappear slowly because of this fact. Natural selection occurs even within the human race. In about 300 years or so… the number of men could become a serious problem.
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