Flu jabs may not protect fat people from infection, a new study suggests.
Experiments found the vaccines protected lean mice against viruses - but did not work as well on obese rodents.
Overweight animals were more susceptible to the virus, which penetrated more deeply into their lungs, making it harder to repair the damage caused.
The findings raise concerns about the effectiveness of vaccines in obese humans who are known to be at a raised risk of suffering severe flu.
Obese people are more likely to be hospitalised or die of a flu infection - and vaccines are the front line defence in combating epidemics of the virus.
The World Health Organization estimates that globally, 10 per cent of adults worldwide and 42 million children under the age of 5 now qualify as obese.
And these numbers expected to grow, while scientists also fears a future pandemic caused by bird flu or other strains that jump species.
The lead author Dr Stacey Schultz-Cherry, of St Jude Children's Research Hospital, said: 'This is the first study to show that current strategies to bolster the effectiveness of flu vaccines protected lean mice from serious illness but fell short of protecting obese mice from infections.
'There is a critical public health need to translate these findings to humans and understand vaccine response in this growing segment of the population.'
The strategies include increasing the vaccine dose and adding substances called adjuvants to them, which enhance the body's immune response.
In the study, researchers used vaccines prepared from killed viruses that are the basis of flu shots.
The vaccines targeted A H1N1 seasonal flu strain, which was the most common cause of flu in 2009.
It was also associated with the 1918 outbreak known as the Spanish Flu, and bird flu strain A(H7N9).
Scientists looked at the immune response of both lean and obese mice after they received a vaccine.
This included looking at how different doses and different adjuvants changed that response.
These methods are used to improve the effectiveness of vaccines in adults and high risk groups.
While adjuvants improved the immune response to vaccinations in both lean and obese mice, the overall immune response was reduced in the obese animals.
Following vaccination, the obese mice had lower levels of antibodies - immune cells that fight off infections - and higher levels of the virus.
And lean mice who received vaccines with adjuvants were protected from severe flu infections while obese mice were not.
Dr Schultz-Cherry said: 'The addition of adjuvants to the vaccines led to levels of neutralising antibodies in both the lean and obese mice that have been considered to be protective.
'Surprisingly that did not translate into protection from flu infection or fatal disease in the obese animals.'
She a suggested obese individuals may be at risk of flu infections even if there are levels of antibodies in their blood that reach what have previously been considered protective levels.
A four-fold increase in the dose of A(H7N9) vaccine bolstered the immune response in both lean and obese mice, but failed to protect the heavier animals from flu-related deaths.
Protective antibodies from lean mice also failed to protect obese mice from flu infections.
Dr Erik Karlsson, a staff scientist in the Schultz-Cherry laboratory, said: 'That suggests the problem lies with the immune response of the obese animals rather than the antibodies themselves.'
The obese mice seemed more susceptible to the virus; levels of it remained elevated after vaccination, when compared to levels of the virus in the blood of lean animals.
Dr Schultz-Cherry said: 'The virus penetrates more deeply into the lungs of obese mice, and the animals seem to have a more difficult time repairing the damage.'
The study was published in the scientific journal mBio.