Vaccines are an important and societally relevant biology topic, but it is unclear how much college biology students know about how vaccines work and what inaccurate ideas they have about that process. Therefore, we asked more than 600 college students taking biology courses at various levels to explain, "How does a vaccine work?" in a free-response format. Based on authoritative sources and responses from immunology and other biology faculty, we created a rubric to gauge the basic knowledge and accuracy present in student responses. Basic knowledge was defined as knowing that vaccines mimic the pathogen, elicit an active immune response, and provide protection against future infection. Accuracy was defined as the absence of scientifically inaccurate ideas. We found that advanced biology majors score significantly higher in basic knowledge and accuracy when compared with all other student groups, but there were no differences between entering biology majors, pre-health majors, and non-pre-health majors. We also uncovered a variety of inaccurate ideas, with the most common being that vaccines contain the original, unmodified pathogen. These results provide a new way to gauge college student understanding of how a vaccine works and enrich our understanding of what college students know about this process.