Analyzing immune responses to varied mRNA and protein vaccine sequences

Hyeong Jun Park, Yoo Jin Bang, Sung Pil Kwon, Woori Kwak, Sang In Park, Gahyun Roh, Seo Hyeon Bae, Jae Yong Kim, Hye Won Kwak, Yongkwan Kim, Soyeon Yoo, Daegeun Kim, Gyochang Keum, Eun Kyoung Bang, So Hee Hong, Jae Hwan Nam

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination, especially mRNA and protein-based vaccines. We developed a new mRNA vaccine encoding the hemagglutinin (HA) glycoprotein of the influenza virus using the 3′-UTR and 5′-UTR of muscle cells (mRNA-HA) and tested its efficacy by heterologous immunization with an HA protein vaccine (protein-HA). The results demonstrated higher IgG2a levels and hemagglutination inhibition titers in the mRNA-HA priming/protein-HA boosting (R-P) regimen than those induced by reverse immunization (protein-HA priming/mRNA-HA boosting, P-R). After the viral challenge, the R-P group showed lower virus loads and less inflammation in the lungs than the P-R group did. Transcriptome analysis revealed that the heterologous prime-boost groups had differentially activated immune response pathways, according to the order of immunization. In summary, our results demonstrate that the sequence of vaccination is critical to direct desired immune responses. This study demonstrates the potential of a heterologous vaccination strategy using mRNA and protein vaccine platforms against viral infection.

Original languageEnglish
Article number84
Journalnpj Vaccines
Issue number1
StatePublished - Dec 2023

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