Sustainable response to DS-Cav1 in healthy volunteers

Ruckwardt TJ, Morabito KM, Phung E, Crank MC, Costner PJ, Holman LA, Chang LA, Hickman SP, Berkowitz NM, Gordon IJ, Yamshchikov GV, Gaudinski MR, Lin B, Bailer R, Chen M, Ortega-Villa AM, Nguyen T, Kumar A, Schwartz RM, Kueltzo LA, Stein JA, Carlton K, Gall JG, Nason MC, Mascola JR, Chen G, Graham BS, VRC 317 study team
The Vaccine Research Center of NIH published a randomized, open-label, dose-escalation phase 1 clinical trial of the DS-Cav1 stabilized pre-F subunit vaccine. 95 healthy adults were vaccinated with different dosages and with or without aluminium hydroxide adjuvant. During the 44 weeks follow-up, the DS-Cav1 vaccine was found to be safe and well tolerated. After an initial high vaccine response in RSV F-protein specific antibodies, sustained neutralizing activity against both RSV subtypes A and B was found across all dosage groups with no or only marginal differences between doses and no effect of the aluminium hydroxide adjuvant. Although a second immunization at week 12 was associated with initially higher neutralizing activity, it did not significantly impact the sustainability of the antibody response at week 44 compared to a single immunization. In addition, the vaccine induced an elevation of pre-F-specific IgG and IgA in the nasopharyngeal mucosa. These results give hope for RSV vaccine development and may have predictive value for the ongoing phase 3 trials with RSV pre-F subunit vaccines in pregnant women.