People tend to read health articles that have gone viral online. A large portion of online popular vaccine articles are against vaccines, which lead to increased exemption rates and recent outbreaks of vaccine-preventable diseases. Since anti-vaccine articles’ themes and persuasive strategies change fast, their effects on viewers’ behaviors may change over time. This study examined how pro- and anti-vaccine topics and public interests have changed from 2007 to 2017. Computational methods (e.g., topic modeling) were used to analyze 923 online vaccine articles and over 4 million shares, reactions, and comments that they have received on social media. Pro-vaccine messages (PVMs) that used personal stories received the most heated discussion online and pure scientific knowledge received the least attention. PVMs that present vaccine disagreements and limitations were not popular. These findings indicate the importance of narratives and directly attacking opposing arguments in health message design. Anti-vaccine messages (AVMs) that discussed flu shots and government conspiracy received the most attention. Since April 2015, even though more PVMs appeared online, AVMs, especially those about vaccine damage, were increasingly more popular than PVMs. Some social events and disease outbreaks might contribute to the popularity of AVMs. Newly emerged anti-vaccine topics (e.g., false rumors of CDC conspiracy) should be noted. This study shows that certain topics can be more popular online and can potentially reach a larger population. It also reveals the evolution of vaccine-related topics and public’s interest. Findings can help to design effective interventions and develop programs to track and combat misinformation.