Effect of T cell vaccine in an influenza human challenge model

The protection afforded by inactivated influenza vaccines can
theoretically be improved by inducing T-cell responses to conserved
internal influenza A antigens. We hypothesized that in an
influenza-controlled human infection challenge, susceptible individuals
receiving a vaccine boosting T cell responses would exhibit lower viral
load and decreased symptoms compared to placebo recipients. Healthy
European volunteers with microneutralization titers < 20 to the
H3N2 challenge strain were randomized double-blind using a permuted-block
list with a 3:2 allocation ratio to receive IM MVA expressing H3N2 NP and
M1 or placebo. Over six weeks later, participants were challenged
intranasally. Nasal swabs were collected twice daily for viral PCR, and
symptoms of influenza were recorded through day 11. T-cell responses were
monitored both pre- and post-vaccination (0,8, and 28 days) and challenge
(0 and 28 days) by ELISpot and multiparameter flow cytometry. There was no
significant effect of NVANP+M1 versus placebo on the viral area under the
curve (vAUC), symptom scores, individual symptoms, or influenza-like
illness in Intent to treat or Protocol Analysis. The MVA-NP+M1 vaccine was
well-tolerated and induced three-fold increases in CD4+ and CD8+ T cell
responses, with no change in the placebo group (p = <0.001). There
was also no correlation between vAUC or symptoms with any of the
pre-challenge CD4+ or CD8+ T-cell phenotypes in either vaccinated or
placebo participants. The use of an MVA vaccine to expand CD4+ and CD8+ T
cells to conserved influenza A antigens in peripheral blood did not impact
outcomes in an influenza H3N2 challenge model in seronegative, healthy
adults.