The DS-Cav1 vaccination for respiratory syncytial virus (RSV) has been shown to be safe and well tolerated, eliciting a robust boost in RSV F-specific antibodies and neutralizing activity that was sustained above baseline for at least 44 weeks, according to the results of a phase 1 clinical trial published in the Lancet Respiratory Medicine.
Researchers conducted the randomized, open-label, dose-escalation VRC 317 phase 1 clinical trial (ClinicalTrials.gov Identifier: NCT03049488) to evaluate the efficacy and safety of the pre-F subunit vaccine DS-Cav1 at a single US site. They sought to explore the safety and immunogenicity of DS-Cav1 — a prefusion F subunit vaccine — in healthy adults between 18 and 50 years of age (N=95). All of the study participants were assigned to receive escalating doses of 50 µg, 150 µg, or 500 µg DS-Cav1 at weeks 0 and 12, and were randomly assigned in a 1:1 ratio within each dose group, with or without aluminum hydroxide (AIOH) adjuvant.: group 1: 50 µg (n=15); group 2: 50 µg + AIOH (n=15); group 3: 150 µg (n=20); group 4: 150 µg + AIOH (n=15); group 5: 500 µg (n=15); and group 6: 500 µg + AIOH (n=15).
The primary study objectives evaluated the tolerability and safety at each dose within 28 days following every injection. Secondary exploratory objectives included neutralizing activity and RSV F-binding antibodies, which were assessed from week 0 to week 44. Safety was evaluated in all of the participants who received at least 1 vaccine dose.
Vaccination with DS-Cav1 elicited robust neutralizing activity and binding antibodies at 4 weeks following administration of a single vaccine (P <.0001 for both F-binding and neutralizing antibodies). At week 44, RSV A neutralizing activity was 3.1-fold above baseline in the 50-µg group, 3.8-fold above baseline in the 150-µg group, and 4.5-fold above baseline in the 500-µg group (P <.0001). Further, RSV B neutralizing activity was 2.8-fold above baseline in the 50-µg group, 3.4-fold above baseline in the 150-µg group, and 3.7-fold above baseline in the 500-µg group (P <.0001).
Pre-F-binding immunoglobulin G (IgG) remained significantly 3.2-fold above baseline in the 50-µg group, 3.4-fold above baseline in the 150-µg group, and 4.0-fold above baseline in the 500-µg group (P <.0001). At week 44, pre-F-binding IgA remained 4.1-fold above baseline in the 50-µg group, 4.3-fold above baseline in the 150-µg group, and 4.8-fold above baseline in the 500-µg group (P <.0001).
No long-term effects were reported with respect to the number of vaccinations, the dose, or adjuvant or neutralizing antibodies. DS-Cav1 was safe and well tolerated, with no serious vaccine-associated adverse events reported.
The researchers concluded that a single low-dose of pre-F immunization of antigen-experienced individuals might have the ability to confer protection that persists throughout an entire RSV season. These findings may be of particular importance in the vaccination of healthy pregnant women, suggesting that higher doses of antigen and adjuvant are unnecessary to provide sustained neutralizing activity conferred by pre-F stabilized immunogens. These findings also may be relevant for vaccines against other enveloped viruses, such as the SARS-CoV-2 spike protein as a COVID-19 vaccine.
Disclosures: Two study authors are inventors on patents for the stabilization of the RSV F protein.
Ruckwardt TJ, Morabito KM, Phung E, et al; for the VRC 317 study team. Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial. Lancet Respir Med. Published online April 14, 2021. doi:10.1016/S2213-2600(21)00098-9