Production and Clinical Evaluation of Norwalk GI.1 Virus Lot 001-09NV in Norovirus Vaccine Development

• Published in: The Journal of infectious diseases Vol. 221; no. 6; pp. 919 - 926
• Main Authors: Mateo, Roberto, Lindesmith, Lisa C, Garg, Shaily J, Gottlieb, Keith, Lin, Karen, Said, Sara, Leon, Juan S, Sims, Amy C, Weber, David J, Baric, Ralph S, Tucker, Sean N, Taylor, David N
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 02.03.2020
• Subjects: Adolescent; Adult; Caliciviridae Infections - prevention & control; Caliciviridae Infections - virology; clinical examination; Female; Gastroenteritis; Gastroenteritis - prevention & control; Gastroenteritis - virology; human diseases; Humans; Immune response; Immunoglobulin A; Immunoglobulin G; Infections; Leukocytes (mononuclear); Major and Brief Reports; Male; Middle Aged; Norovirus; Norwalk virus; Norwalk virus - classification; Peripheral blood mononuclear cells; Vaccine development; Vaccine efficacy; Vaccines; Viral Vaccines - immunology; Virulence; viruses; Young Adult; human challenge study; human norovirus; antibody-secreting cells; controlled human infection model; blockade antibody
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz540

Abstract Background Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM). Methods A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses. Results Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells. Conclusions GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates. A new robust platform for the purification of a novel GI.1 human norovirus stock, Lot 001-09NV, produced an infectious inoculum that can be used to compare and standardize immune response levels and efficacy of future norovirus vaccine candidates.