Novavax, Inc. today announced positive top-line safety and immunogenicity data for its respiratory syncytial virus (RSV) vaccine candidate from a dose-ranging Phase 1 study in elderly adults. All subject groups receiving the recombinant fusion (F) protein nanoparticle vaccine candidate exhibited antibody responses against RSV at 28 and 56 days post-immunization, with rises in serum anti-F immunoglobulin G (IgG) antibody levels.
The highest response rates and greatest increases in antibody levels were observed in groups receiving RSV F antigen with aluminum phosphate as an adjuvant. All subjects simultaneously received a licensed seasonal trivalent influenza vaccine to ensure coverage over the influenza season. Local and systemic safety were monitored and together with the interim immunogenicity are provided here as top line data through Day 56.
The study examined the immunogenicity and safety of Novavax’s RSV F nanoparticle vaccine in 220 healthy elderly adults (≥60 years of age, mean age of 68 years of age). Subjects received either 60μg or 90μg of the RSV F vaccine candidate, with or without adjuvant, or a placebo. The vaccine was well tolerated with no meaningful differences in the frequencies of adverse events (AEs) between the placebo (70%) and active vaccine groups (58-75%), and no dose-related trends in AEs. The adjuvant groups had a higher incidence rate of injection site AEs (43%) compared to placebo (23%), but all such AEs were reported as mild or moderate in severity. There were no vaccine-related serious AEs, and no subject withdrawals due to AEs.
Highlights of the interim immunogenicity results of the RSV F vaccine in elderly adults include:
The overall immune responses, in terms of both frequency and amplitude of antibody rises, were greater in the groups receiving the 90μg dose of RSV F vaccine compared to the groups dosed with 60μg. Significantly greater immune responses were observed in the groups receiving adjuvanted vaccine compared to those receiving unadjuvanted formulations.
Increases in anti-F IgG were observed in all actively-vaccinated groups by Day 7 post-immunization. Antibody levels continued to rise through Day 28 among recipients of unadjuvanted vaccines, then plateaued. In contrast, anti-F IgG levels continued to rise through Day 56 in recipients of adjuvanted vaccine. The greatest response was observed in the 90μg RSV F adjuvanted vaccine group, with a 5.6 fold rise in anti-F IgG and a sero-response rate of 79% at Day 56.
Antibodies competing with palivizumab, a monoclonal antibody known to be efficacious in the prevention of severe RSV disease, were essentially undetectable in these elderly subjects at Day 0, but showed significant increases in 80 to 97% of active vaccine recipients by Day 28. In subjects receiving the adjuvanted vaccines, significant responses were sustained in 97% through Day 56. In the subjects receiving the 90μg RSV F vaccine with adjuvant, levels of competitive antibodies equivalent to 186μg/mL of palivizumab were achieved.
Levels of antibodies specific for the antigenic site II peptide, representing the neutralizing epitope on the RSV F protein recognized by palivizumab, rose 5.6 to 12.5-fold, with best responses again in the 90μg RSV F adjuvanted vaccine group.
RSV A and B microneutralizing antibody levels increased in all vaccinated subject groups, with greatest responses seen in the 90μg RSV F adjuvanted vaccine group. Geometric mean-fold increases in microneutralizing antibody titers ranged from 1.4 to 1.7-fold.
Hemagglutination-inhibiting (HAI) responses to the seasonal influenza vaccine were unaffected by co-administration with the RSV F vaccines; an important feature given that the two vaccines would likely be given to the elderly contemporaneously in clinical practice.
“These data provide further evidence that our RSV F nanoparticle vaccine is well-tolerated and immunogenic,” said Gregory Glenn, Chief Medical Officer of Novavax. “As seen in our previous trials in younger subjects, the vaccine induced an important functional immune response in the palivizumab-like antibodies, as well as enhancing microneutralization antibodies to levels that are in excess of the range expected to reduce hospitalizations resulting from RSV. In addition, the co-administration of the RSV F vaccine candidate with a licensed seasonal influenza vaccine did not appear to negatively impact or interfere with induction of immunity in the influenza vaccine.”
“Protecting the elderly from respiratory ailments is an important part of both our RSV and our seasonal influenza vaccine development programs,” noted Stan Erck, President and CEO of Novavax. “These data suggest a path forward for a Novavax combination RSV and seasonal influenza vaccine to improve the coverage for respiratory infections in elderly and high-risk adults.”