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Publication Abstract from PubMed

An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV.

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.,Mukhamedova M, Wrapp D, Shen CH, Gilman MSA, Ruckwardt TJ, Schramm CA, Ault L, Chang L, Derrien-Colemyn A, Lucas SAM, Ransier A, Darko S, Phung E, Wang L, Zhang Y, Rush SA, Madan B, Stewart-Jones GBE, Costner PJ, Holman LA, Hickman SP, Berkowitz NM, Doria-Rose NA, Morabito KM, DeKosky BJ, Gaudinski MR, Chen GL, Crank MC, Misasi J, Sullivan NJ, Douek DC, Kwong PD, Graham BS, McLellan JS, Mascola JR Immunity. 2021 Apr 13;54(4):769-780.e6. doi: 10.1016/j.immuni.2021.03.004. Epub , 2021 Apr 5. PMID:33823129^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.