DS-Cav1 beats previous subunit RSV vaccines

Crank MC, Ruckwardt TJ, Chen M, Morabito1 KM, Phung E, Costner PJ, Holman LA, Hickman SP, Berkowitz NM, Gordon IJ, Yamshchikov GV, Gaudinski MR, Kumar A, Chang LA, Moin SM, Hill JP, DiPiazza AT,  Schwartz RM, Kueltzo1 L, Cooper JW, Chen P, Stein JA, Carlton1 K, Gall JG, Nason MC, Kwong PD, Chen1 GL, Mascola JR,McLellan JS, Ledgerwood JE, Graham BS, the VRC 317 Study Team

This RSV subunit vaccine has smoothly passed the first hurdle in clinical development. DS-Cav1 is stabilized trimer of the prefusion conformation of the RSV-F protein. The vaccine was clinically evaluated by the same researchers of the Vaccine Research Center (VRC) of the Nation Institute of Health (NIH) only a few years after demonstrating the existence of the prefusion and postfusion RSV-F variants. Immunogenicity of this apparently safe vaccine was tested in a diverse group of 40 healthy adults up to 12 weeks after vaccination. Remarkably, the vaccine resulted in an increase in neutralization that was larger than the increase in binding to RSV F. Twelve weeks after vaccination, neutralization of RSV A was still increased 5 to 10-fold, while a 3 to 5-fold increase in RSV B neutralization was observed. The boost of neutralization was mediated by antibodies against preF and shared pre/post F epitopes, but not by antibodies against epitopes only present at postF. Using preF and postF probes, the authors show that the vaccine elicits a boost in memory preF B-cells, but not postF B-cells. Taken together, DS-Cav1 shows superiority to previous subunit vaccines by inducing higher levels of neutralizing antibodies with a relatively low induction of non-neutralizing antibodies.

Download Paper of the Month | September 2019