RSV Vaccine Candidate DS-Cav1 Shows Early Promise in Phase 1 Trial

Each year respiratory syncytial virus (RSV) leads to 57,527 hospitalizations among children under 5 years and 177,000 hospitalizations among adults over the age of 65 years, according to the US Centers for Disease Control and Prevention.

But now, hope may be on the horizon as the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has announced promising results from a phase 1 clinical trial evaluating a novel experimental vaccine.

"A vaccine to prevent RSV is a long-sought goal that has eluded us for decades," Anthony S. Fauci, MD, director of NIAID, said in a press release. "The early results of this trial suggest that this structure-based strategy for developing an RSV vaccine may bring that goal within reach."

The vaccine candidate DS-Cav1 was engineered by researchers at NIAID who sought to develop a vaccine that could stimulate neutralizing antibodies. To accomplish this, the investigators determined atomic-level structures of the surface protein fusion (F) glycoprotein in both its rearranged postfusion and functional prefusion states.

The team found that the epitopes with the best chance of eliciting strong-binding neutralizing antibodies are displayed during prefusion but are lost once the F protein begins the transformation into the irreversible postfunction state.

Using this information, a team of scientists used structural engineering techniques to stabilize the F protein in its prefusion shape. In 2013, they used multiple versions of a vaccine in mouse and nonhuman primate models. The most promising vaccine candidate was selected for clinical evaluation and subsequently manufactured for clinical testing.

A report, published in the journal Science, details an interim analysis showing that 1 dose of the investigational vaccine led to increases in RSV-neutralizing antibodies that were sustained for several months.

The report includes data from the first 40 healthy adult volunteers enrolled in the trial. Participants in the study received a dose of either 50 or 150 micrograms (μg) of DS-Cav1. According to the investigators, half the volunteers received the vaccine with an alum adjuvant and half received unadjuvanted vaccine.

Four weeks after vaccination, the levels of RSV-neutralizing antibodies in participants who received 50 μg of vaccine (with or without alum) increased 7-fold over the levels present prior to vaccination. Further, 1 dose of 150 μg (without alum) boosted neutralizing antibody levels 12-fold and 1 dose of alum-adjuvanted vaccine resulted in a 15-fold surge in neutralizing antibodies.

The investigators further note that at 12 weeks, neutralizing antibodies remained 5- to 10-fold above baseline levels in all vaccine dosage groups.

"Compared to previous RSV subunit vaccines, the DS-Cav1 vaccine candidate elicits neutralizing antibodies with a superior functional profile, providing the basis for the next steps in developing an effective vaccine against RSV," said Barney S. Graham, MD, PhD, a scientist with NIAID’s Vaccine Research Center. "The clinical data from this trial demonstrate the feasibility of using information about viral protein structure to rationally design vaccines and represents an important step toward a future of precision vaccines."