Norovirus vaccine against experimental human Norwalk virus illness

Robert L. Atmar, David I. Bernstein, Clayton D. Harro, Mohamed S. Al-Ibrahim, Wilbur H. Chen, Jennifer Ferreira, Mary K. Estes, David Y. Graham, Antone R. Opekun, Charles Richardson, Paul M. Mendelman

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial to assess the safety, immunogenicity, and efficacy of an investigational, intranasally delivered norovirus viruslike particle (VLP) vaccine (with chitosan and monophosphoryl lipid A as adjuvants) to prevent acute viral gastroenteritis after challenge with a homologous viral strain, Norwalk virus (genotype GI.1). Healthy adults 18 to 50 years of age received two doses of either vaccine or placebo and were subsequently inoculated with Norwalk virus and monitored for infection and gastroenteritis symptoms. RESULTS: Ninety-eight persons were enrolled and randomly assigned to receive vaccine (50 participants) or placebo (48 participants), and 90 received both doses (47 participants in the vaccine group and 43 in the placebo group). The most commonly reported symptoms after vaccination were nasal stuffiness, nasal discharge, and sneezing. Adverse events occurred with similar frequency among vaccine and placebo recipients. A Norwalk virus-specific IgA seroresponse (defined as an increase by a factor of 4 in serum antibody levels) was detected in 70% of vaccine recipients. Seventy-seven of 84 participants inoculated with Norwalk virus were included in the per-protocol analysis. Vaccination significantly reduced the frequencies of Norwalk virus gastroenteritis (occurring in 69% of placebo recipients vs. 37% of vaccine recipients, P = 0.006) and Norwalk virus infection (82% of placebo recipients vs. 61% of vaccine recipients, P = 0.05). CONCLUSIONS: This norovirus VLP vaccine provides protection against illness and infection after challenge with a homologous virus. (Funded by LigoCyte Pharmaceuticals and the National Institutes of Health; ClinicalTrials.gov number, NCT00973284.)

Original languageEnglish (US)
Pages (from-to)2178-2187
Number of pages10
JournalNew England Journal of Medicine
Volume365
Issue number23
StatePublished - Dec 8 2011

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Norwalk virus
Norovirus
Vaccines
Placebos
Gastroenteritis
Virus Diseases
Nose
Vaccination
Sneezing
National Institutes of Health (U.S.)
Chitosan
Infection
Immunoglobulin A
Multicenter Studies

ASJC Scopus subject areas

  • Medicine(all)

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Atmar, R. L., Bernstein, D. I., Harro, C. D., Al-Ibrahim, M. S., Chen, W. H., Ferreira, J., ... Mendelman, P. M. (2011). Norovirus vaccine against experimental human Norwalk virus illness. New England Journal of Medicine, 365(23), 2178-2187.

Norovirus vaccine against experimental human Norwalk virus illness. / Atmar, Robert L.; Bernstein, David I.; Harro, Clayton D.; Al-Ibrahim, Mohamed S.; Chen, Wilbur H.; Ferreira, Jennifer; Estes, Mary K.; Graham, David Y.; Opekun, Antone R.; Richardson, Charles; Mendelman, Paul M.

In: New England Journal of Medicine, Vol. 365, No. 23, 08.12.2011, p. 2178-2187.

Research output: Contribution to journalArticle

Atmar, RL, Bernstein, DI, Harro, CD, Al-Ibrahim, MS, Chen, WH, Ferreira, J, Estes, MK, Graham, DY, Opekun, AR, Richardson, C & Mendelman, PM 2011, 'Norovirus vaccine against experimental human Norwalk virus illness', New England Journal of Medicine, vol. 365, no. 23, pp. 2178-2187.
Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen WH, Ferreira J et al. Norovirus vaccine against experimental human Norwalk virus illness. New England Journal of Medicine. 2011 Dec 8;365(23):2178-2187.
Atmar, Robert L. ; Bernstein, David I. ; Harro, Clayton D. ; Al-Ibrahim, Mohamed S. ; Chen, Wilbur H. ; Ferreira, Jennifer ; Estes, Mary K. ; Graham, David Y. ; Opekun, Antone R. ; Richardson, Charles ; Mendelman, Paul M. / Norovirus vaccine against experimental human Norwalk virus illness. In: New England Journal of Medicine. 2011 ; Vol. 365, No. 23. pp. 2178-2187.
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AU - Estes, Mary K.

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AU - Richardson, Charles

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N2 - BACKGROUND: Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial to assess the safety, immunogenicity, and efficacy of an investigational, intranasally delivered norovirus viruslike particle (VLP) vaccine (with chitosan and monophosphoryl lipid A as adjuvants) to prevent acute viral gastroenteritis after challenge with a homologous viral strain, Norwalk virus (genotype GI.1). Healthy adults 18 to 50 years of age received two doses of either vaccine or placebo and were subsequently inoculated with Norwalk virus and monitored for infection and gastroenteritis symptoms. RESULTS: Ninety-eight persons were enrolled and randomly assigned to receive vaccine (50 participants) or placebo (48 participants), and 90 received both doses (47 participants in the vaccine group and 43 in the placebo group). The most commonly reported symptoms after vaccination were nasal stuffiness, nasal discharge, and sneezing. Adverse events occurred with similar frequency among vaccine and placebo recipients. A Norwalk virus-specific IgA seroresponse (defined as an increase by a factor of 4 in serum antibody levels) was detected in 70% of vaccine recipients. Seventy-seven of 84 participants inoculated with Norwalk virus were included in the per-protocol analysis. Vaccination significantly reduced the frequencies of Norwalk virus gastroenteritis (occurring in 69% of placebo recipients vs. 37% of vaccine recipients, P = 0.006) and Norwalk virus infection (82% of placebo recipients vs. 61% of vaccine recipients, P = 0.05). CONCLUSIONS: This norovirus VLP vaccine provides protection against illness and infection after challenge with a homologous virus. (Funded by LigoCyte Pharmaceuticals and the National Institutes of Health; ClinicalTrials.gov number, NCT00973284.)

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