Prophylactic Lalba mRNA-LNP vaccination prevents the progression of early breast lesions

Here, we developed lipid nanoparticle (LNP)-encapsulated mRNA vaccines expressing the alpha-lactalbumin (LALBA) protein unique to mammary luminal progenitors/alveolar-like cells. Vaccination of outbred Sprague-Dawley rats with N1-methylpseudouridine-modified or unmodified Lalba mRNA-LNP induced different degrees of LALBA-specific and non-specific immune response.

While the vaccination caused no detectable toxicity in normal mammary glands or other organs, it suppressed Nitroso-N-methylurea (NMU)-induced tumorigenesis and enhanced the tumor-free survival. Single-cell transcriptomic analysis revealed that vaccination leads to the reduction of a distinct proliferative luminal progenitor population in immunoreactive early lesions. Overall, we demonstrated that prophylactic use of Lalba mRNA-LNP has the potential to suppress the initiation and progression of early breast lesions.