A broad-spectrum peptide vaccine candidate, FLU-v, reduced the risk of mild-to-moderate influenza disease (MMID) in healthy volunteers in a phase 2 challenge study. "This report follows a recent publication of positive FLU-v phase 2b field study results demonstrating immunogenicity in 175 individuals," Dr. Olga Pleguezuelos of SEEK Central Point in London, UK told Reuters Health by email. (http://bit.ly/39DiGhK) "The data from both studies put together demonstrate that the T-cell strategy employed by FLU-v has the potential to offer protection against influenza infection as a vaccine," she said, "and that larger studies are now needed to evaluate how the vaccine interacts with influenza strains in different cohorts in a real-world setting." As reported in npj Vaccines, 153 healthy adults were randomized to receive one or two doses of adjuvanted FLU-v or adjuvanted placebo subcutaneously on days -43 and -22 before an intranasal challenge on day 0 with the A/California/04/2009/H1N1 challenge virus. The main objective was a reduction in MMID, defined as the presence of viral shedding and clinical influenza symptoms. Participants who received a single dose of adjuvanted FLU-v were significantly less likely to develop MMID after the challenge compared with placebo: 32.5% vs 54.8%, respectively. By contrast, 36.6% of those in the two-dose group developed MMID. Overall, the vaccine was well tolerated. After vaccination, but before the influenza challenge, 64% of participants experienced an adverse event (AE). AEs were similar in the single dose and placebo groups (55.8% vs. 54%); the largest number was observed in the two-dose adjuvanted FLU-v group, at 82.4%. No vaccine-related AEs were observed after the challenge. Dr. Pleguezuelos noted, "We tested one and two doses to confirm that no benefit was gained by giving an additional dose. Administration of an antigen numerous times is preferred when antibody responses are sought. However, the aim of FLU-v is not to develop antibody responses but to trigger cellular responses characterized by activation of lymphocytes (T-cells)." "Often, repetitive administrations of the antigen in a short period of time can be detrimental, as rather than increase the stimulation of T-cells, it induces tolerance or exhaustion of this cell type," she said. "This explains why in this study, the one-dose arm is more efficacious than the two-dose arm; but still, both performed better than placebo." Dr. John Sanders, Chief of Infectious Diseases at Wake Forest Baptist Health in Winston-Salem, NC called the study "intriguing." "The results should be viewed very positively as another step towards reaching the goal of a universal vaccine that elicits long term immunity," he told Reuters Health by email. "However, it was a small study composed of otherwise healthy, young adults. They were challenged with only one vaccine strain. The level of protection, while reaching statistical significance for protection against MMID, was modest in the one-dose group and did not even reach statistical significance in the two-dose group." "Therefore, while I agree with the authors' conclusions that it is encouraging to see that a vaccine eliciting cell-mediated immunity against conserved regions of influenza can offer some protection against infection, further development of this vaccine may be necessary to improve protection and further studies will be needed to determine if it can provide protection against multiple influenza strains," he said. "Again, this is a positive step but more work needs to be done." —Marilynn Larkin Source
