Knowledge of mechanisms of infection in vulnerable populations is needed in order to prepare for future outbreaks. Here, using a unique dataset collected during a 2009 outbreak of influenza A(H1N1)pdm09 in a university town, we evaluated mechanisms of infection and identified that an epidemiological model containing partial protection of susceptibles best describes H1N1 dynamics in a rural university environment. We found that the protected group was over 14 times less susceptible to H1N1 infection than unprotected susceptibles. Our estimates show that the basic reproductive rate, R
0, was 5·96 (95% confidence interval 5·83–6·61), and, importantly, R
0 could be decreased to below 1 and similar epidemics could be avoided by increasing the proportion of the initial protected group. Moreover, several weeks into the epidemic, this protected group generated more new infections than the unprotected susceptible group, and thus, such protected groups should be taken into account while studying influenza epidemics in similar settings.