Abstract Title
Safety, Tolerability, and Immunogenicity of an oral adenovirus-vectored GI.1/GII.4 norovirus vaccine in breastfeeding women: a phase 1, double-blind, randomized placebo-controlled clinical trial
Presenter
James Cummings, VAXART
Co-Author(s)
Molly R. Braun1, Lam-Quynh Nguyen1, Becca A. Flitter1, Nicholas J. Bennett1, Darreann Carmela M. Hailey1, Colin A. Lester1, Elena D. Neuhaus1, Nick P. D’Amato1, Maria D. Apkarian1, Marcela F. Pasetti2, Sean N. Tucker1, and James F. Cummings1
Affiliations:
1 Vaxart, Inc.
2 Center for Vaccine Development, University of Maryland Baltimore School of Medicine
Abstract Category
Vaccines and immunity
Abstract
Norovirus can cause severe and fatal gastroenteritis in infants. A previous attempt to vaccinate infants with an injected vaccine yielded no protective efficacy, possibly due to insufficient mucosal responses. Alternatively, mucosal vaccination of breastfeeding women may facilitate infant protection through breast milk (BM). This study evaluated the safety, tolerability, and immunogenicity of an orally-delivered norovirus vaccine in breastfeeding women.
Breastfeeding women were randomized in a double-blind, placebo-controlled trial in South Africa. Participants received oral VXA-G1.1-NN/VXA-G2.4-NS targeting norovirus GI.1 and GII.4, at 5×1010 infectious units (IU)/strain (medium, n=30), 1×1011 IU/strain (high, n=30), or placebo (n=16). Primary safety outcomes were solicited adverse events (AE) seven days post-vaccination and unsolicited AEs through day 29. Primary immunogenicity outcomes included BM norovirus-specific IgA increases through day 29. Infant stool IgA levels were also assessed.
VXA-G1.1-NN/VXA-G2.4-NS was well-tolerated with favorable safety profiles and no serious vaccine-related AEs. Headache (23.7%) and nausea (15.8%) were most frequently reported in vaccinated participants, similar to placebo. Peak BM GI.1-specific IgA mean fold rise (MFR) were 5.57 and 4.04 (p=0.018) for medium and high dose compared to 1.40 in placebo. Peak BM GII.4-specific IgA MFRs were 2.89 and 5.99 (p=0.004) for medium and high dose compared to 1.08 in placebo. Infant stool norovirus-specific IgA increased up to 806-fold in treatment groups, compared to 6.49 in placebo and was corelated with BM IgA (p
Breastfeeding women were randomized in a double-blind, placebo-controlled trial in South Africa. Participants received oral VXA-G1.1-NN/VXA-G2.4-NS targeting norovirus GI.1 and GII.4, at 5×1010 infectious units (IU)/strain (medium, n=30), 1×1011 IU/strain (high, n=30), or placebo (n=16). Primary safety outcomes were solicited adverse events (AE) seven days post-vaccination and unsolicited AEs through day 29. Primary immunogenicity outcomes included BM norovirus-specific IgA increases through day 29. Infant stool IgA levels were also assessed.
VXA-G1.1-NN/VXA-G2.4-NS was well-tolerated with favorable safety profiles and no serious vaccine-related AEs. Headache (23.7%) and nausea (15.8%) were most frequently reported in vaccinated participants, similar to placebo. Peak BM GI.1-specific IgA mean fold rise (MFR) were 5.57 and 4.04 (p=0.018) for medium and high dose compared to 1.40 in placebo. Peak BM GII.4-specific IgA MFRs were 2.89 and 5.99 (p=0.004) for medium and high dose compared to 1.08 in placebo. Infant stool norovirus-specific IgA increased up to 806-fold in treatment groups, compared to 6.49 in placebo and was corelated with BM IgA (p