Scientists discovered something surprising about how flu vaccines work differently in men and women, especially when people have obesity. Using mice, researchers found that female mice developed stronger protection against the flu after vaccination compared to male mice. This difference was even more noticeable in obese mice—obese males had the weakest vaccine response and got sicker when exposed to the flu virus. The study suggests that biological sex plays an important role in how well flu vaccines work, and this finding could help doctors create better vaccines in the future that work equally well for everyone.
The Quick Take
- What they studied: Whether male and female mice respond differently to flu vaccines, and whether obesity affects this response
- Who participated: Laboratory mice (C57BL/6J strain) divided into groups: males and females, some fed a high-fat diet to become obese and others fed a normal diet as controls
- Key finding: Female mice developed stronger antibody responses to the flu vaccine and were better protected against the flu virus compared to male mice. Obese males had the weakest vaccine response and suffered the most severe illness when exposed to the flu.
- What it means for you: This research suggests that biological sex and weight may influence how well flu vaccines work in people. If confirmed in human studies, doctors might need to adjust vaccine strategies based on these factors. However, this is animal research and more studies in humans are needed before changing medical recommendations.
The Research Details
Researchers used laboratory mice to study how flu vaccines work in males versus females, with some mice being obese and others at normal weight. All mice received two doses of an inactivated flu vaccine (the same type used in humans) given three weeks apart. The scientists then measured how many antibodies (immune proteins) the mice produced and tested their immune cells. About a week after the second vaccine dose, they exposed the vaccinated mice to a live flu virus to see how well the vaccine protected them. They tracked how sick the mice got by monitoring weight loss and checked their lungs for virus levels and inflammation.
This type of study is called a controlled experiment because the researchers carefully controlled which mice got which diet and vaccine, allowing them to isolate the effects of sex and obesity. By using mice, scientists can study immune responses in detail and control variables that would be impossible to control in human studies.
The researchers used several laboratory techniques to measure immune responses: blood tests for antibodies, examination of immune cells from the spleen and bone marrow, lung virus measurements, tissue examination under a microscope, and measurement of immune signaling molecules.
Understanding how sex and obesity affect vaccine responses is important because it could help explain why some people get better protection from vaccines than others. If these findings apply to humans, it could lead to personalized vaccine strategies or improved vaccine designs that work equally well for everyone, regardless of sex or weight status.
This study was published in a peer-reviewed scientific journal (Frontiers in Immunology), meaning other experts reviewed it before publication. The researchers used established laboratory methods and mouse models commonly used in vaccine research. However, this is animal research, so results may not directly apply to humans. The study appears well-designed with appropriate controls and multiple measurements of immune response, which strengthens confidence in the findings.
What the Results Show
Female mice developed significantly higher levels of flu-fighting antibodies in their blood compared to male mice, regardless of whether they were obese or normal weight. When exposed to the flu virus after vaccination, female mice were better protected and showed less severe illness.
Male mice with obesity had the worst outcomes. They produced the lowest antibody levels after vaccination, got sicker when exposed to the flu virus, and their lungs contained higher levels of active virus, meaning their bodies couldn’t clear the infection as effectively. These obese males also showed more inflammation in their lungs.
Interestingly, when researchers looked at immune cells in the spleen and bone marrow, they found similar numbers of B cells (the cells that make antibodies) in both males and females. This suggests the problem in obese males wasn’t a lack of immune cells, but rather that their B cells weren’t working properly to produce antibodies. The female immune cells appeared to function more efficiently even during obesity.
The study found that obesity itself reduced vaccine effectiveness in both sexes, but the effect was much more pronounced in males. Normal-weight males also had weaker responses than normal-weight females, suggesting that sex differences in vaccine response exist independent of obesity. The heightened lung inflammation in obese males correlated with their inability to clear the virus, suggesting that excessive inflammation may have contributed to their worse disease outcomes.
Previous research has shown that biological sex influences immune responses and vaccine effectiveness in non-obese individuals, with females generally mounting stronger responses. However, few studies have examined how obesity affects these sex differences. This research fills that gap by showing that obesity amplifies the existing sex differences, making males particularly vulnerable. The findings align with broader research showing that obesity impairs immune function.
This study used mice, not humans, so results may not directly translate to people. Mice have different immune systems and body compositions than humans. The study used only one mouse strain and one flu vaccine type, so results might differ with other vaccines or mouse populations. The researchers didn’t investigate the specific biological mechanisms explaining why obese males had impaired B cell function. Additionally, the study didn’t examine whether these differences persist over time or with different flu variants.
The Bottom Line
Based on this research alone, no changes to current flu vaccination practices are recommended at this time. However, this study suggests that future vaccine development should consider sex and obesity status as factors. People of all sexes and weights should continue following current flu vaccination guidelines. If you have obesity or other health concerns, discuss personalized vaccine strategies with your healthcare provider. (Confidence level: Low—this is preliminary animal research)
This research is most relevant to vaccine developers, immunologists, and public health officials designing future vaccines. People with obesity and healthcare providers treating them may find this information interesting as it suggests obesity affects immune responses. However, current flu vaccination recommendations remain unchanged for all groups. This research should not discourage anyone from getting vaccinated.
This is basic research in mice, so practical applications for humans are likely years away. If human studies confirm these findings, it could take several more years to develop and test modified vaccines. In the meantime, current vaccines remain the best protection against flu for everyone.
Want to Apply This Research?
- Track flu vaccination dates and any subsequent illness (date, duration, severity) for 6 months post-vaccination to monitor personal vaccine effectiveness over time
- Set a reminder to get annual flu vaccination at the same time each year, and log any side effects or illness patterns to identify personal trends in vaccine response
- Maintain a yearly log comparing vaccination date, timing of any flu-like illness, illness severity (mild/moderate/severe), and duration to track personal vaccine effectiveness patterns across seasons
This research was conducted in mice and has not been tested in humans. These findings do not change current flu vaccination recommendations for any group. All individuals should continue following CDC and healthcare provider guidance regarding flu vaccination. This information is for educational purposes only and should not replace professional medical advice. If you have specific concerns about vaccine effectiveness based on your health status, consult with your healthcare provider.