High Serum Levels of Norovirus Genotype-Specific Blocking Antibodies Correlate With Protection From Infection in Children

Malm, Maria; Uusi-Kerttula, Hanni; Vesikari, Timo; Blazevic, Vesna

doi:10.1093/infdis/jiu361

Cited by 79 publications

(83 citation statements)

References 43 publications

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“…Altogether, the results of this study indicate that measurement of the NoV strain-specific IgG level or the cross-reactive binding antibodies induced by immunization with different NoV VLPs alone is not adequate to determine the quality of immune responses (31,51). This is in line with our results obtained with human serum (30), where genogroup-specific cross-reactive IgG titers were raised after natural NoV infection but no equivalent blocking antibody titer increase was induced.…”

Section: Discussionsupporting

confidence: 77%

“…GII.4 strain NoVs have an exceptionally broad HBGA binding repertoire and high transmissibility (2), explaining the predominance of GII.4 NoV infections worldwide (28). The quantity of genotype-specific antibodies that can block the binding of NoV VLP to the HBGA has been shown to increase remarkably after NoV infection or NoV VLP immunization in humans (18,19,29,30). Prechallenge levels of blocking antibodies in human serum have been shown to positively correlate with the protection of both NoV infection and illness, and it is generally accepted that especially blocking antibodies in serum play a substantive role in protection from NoV infection (18,31).…”

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confidence: 99%

“…However, induction of long-term protective immunity is extremely challenging because of the rapid evolution of NoV strains that result in high genetic variability and insufficient cross-protective immunity, especially between GI and GII NoVs (30,35,36). It is believed that a representative of each genogroup is a minimum requirement for crossprotective NoV vaccine (10,37,38).…”

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confidence: 99%

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Genotype Considerations for Virus-Like Particle-Based Bivalent Norovirus Vaccine Composition

Malm

Tamminen

Lappalainen

et al. 2015

Clin Vaccine Immunol

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Norovirus (NoV) genogroup I (GI) and GII are responsible for most human infections with NoV. Because of the high genetic variability of NoV, natural infection does not induce sufficient protective immunity to different genotypes or to variants of the same genotype and there is little or no cross-protection against different genogroups. NoV-derived virus-like particles (VLPs) are promising vaccine candidates that induce high levels of NoV-specific humoral and cellular immune responses. It is believed that a bivalent NoV vaccine consisting of a representative VLP from GI and GII is a minimum requirement for an effective vaccine. Here, we compared the abilities of monovalent immunizations with NoV GI.1-2001, GI.3-2002, GII.4-1999, and GII.4-2010 New Orleans VLPs to induce NoV type-specific and cross-reactive immune responses and protective blocking antibody responses in BALB/c mice. All of the VLPs induced comparable levels of type-specific serum IgG antibodies, as well as blocking antibodies to the VLPs used for immunization. However, the abilities of different VLP genotypes to induce cross-reactive IgG and cross-blocking antibodies varied remarkably. Our results confirm previous findings of a lack of cross-protective immune responses between GI and GII NoVs. These data support the rationale for including NoV GI.3 and GII.4-1999 VLPs in the bivalent vaccine formulation, which could be sufficient to induce protective immune responses across NoV genotypes in the two common genogroups in humans.

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Section: Discussionsupporting

confidence: 77%

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confidence: 99%

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confidence: 99%

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Genotype Considerations for Virus-Like Particle-Based Bivalent Norovirus Vaccine Composition

Malm

Tamminen

Lappalainen

et al. 2015

Clin Vaccine Immunol

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“…Hence, patients with high serum IgG levels may be especially sensitive to antibiotics. Malm et al reported that patients with a high serum IgG titer can block norovirus infections [13] . Additionally, the effects of vaccination are assessed using serum IgG levels in various infectious diseases.…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum anti-Helicobacter pylori IgG Levels is a Predictor of Successful Eradication Therapy

Shinozaki

Sakamoto

Hayashi

et al. 2015

Journal of Gastroenterology and Hepatology Research

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habits, prior PPI intake, kind of PPI, serum IgG value and degree of atrophy. Univariate analysis showed that high serum IgG significantly predicts successful eradication (odds ratio (OR) 2.583, 95% confidence interval (CI) 1. 285-5.191, p=0.008). The eradication rate was 77% (43/56) in the ≥45 U/mL group and 56% (73/130) in the <45 U/ mL group, and significance was confirmed by multivariate analysis (OR 2.626, 95% CI 1. 269-5.436, p=0.009). Multivariate analysis showed a trend that advanced age (≥70 year-old) increased the rate of successful eradication (OR 1.669, p=0.132 INTRODUCTIONHelicobacter pylori (H. pylori) eradication is the standard treatment for preventing gastric ulcers and cancer throughout the world. In Japan, H. pylori eradication therapy for H. pylori gastritis has been approved by the National Health Insurance system since February 2013. For primary eradication therapy, triple drug therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin for one week is the approved regimen. Despite more patients undergoing this eradication regimen in Japan, the success rate of primary H. pylori eradication has been decreasing over the last decade because of emerging antibiotic resistance [1] . To identify a predictor of successful primary Helicobacter pylori (H. pylori) eradication assessed in routine clinical practice. METHODS: From February 2013 to January 2015, 186 patients underwent primary eradication therapy. We retrospectively reviewed the medical records. All patients underwent EGD before eradication therapy and H. pylori infection was diagnosed by ≥10 U/mL serum anti-H. pylori IgG. We used standard triple therapy including a proton pump inhibitor (PPI) (rabeprazole 10 mg or lansoprazole 30 mg), clarithromycin 200 mg and amoxicillin 750 mg twice daily for seven days. To determine if eradication succeeded, a 13 C-urea breath test was performed on all patients more than eight weeks after primary eradication. RESULTS: The overall success rate of H. pylori eradication therapy was 62% (116/186). We assessed potential predictors of successful primary H. pylori eradication therapy including gender, age, smoking

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“…58 The same group reported the generation of anti-GII.4 antibodies following infection among children less than 2 y old targeting closely related genotypes. 59,60 More than 90% of individuals are seropositive to NoV by the time they reach adulthood; however, the role of pre-existing immunity is still not fully understood when related to protection or reducing the risk of acquiring new NoV infections. 15 The fact that asymptomatic infection occurs at an early age as reported by outbreak and human challenge studies 48,[61][62][63] provides critical insight to the potential reservoir of transmission at an early age and its clear implication on the need for an effective vaccine.…”

Section: Viral Shedding Natural Infection With Nov and Seroprotectionmentioning

confidence: 99%

Norovirus vaccines: Correlates of protection, challenges and limitations

Melhem

2016

Human Vaccines & Immunotherapeutics

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Norovirus (NoV) is responsible for at least 50% of all gastroenteritis outbreaks worldwide. NoVs are classified into 6 different genogroups (GGI-GGVI) based on the viral capsid protein with NoV genogroup II genotype 4 (GII.4) being the predominant strain causing human diseases. Supportive therapy involving reversal of dehydration and electrolyte deficiency is the main treatment of NoV gastroenteritis. However, the worldwide increased recognition of NoV as an important agent of diarrheal gastroenteritis prompted researchers to focus on establishing preventive strategies conferring long-lasting immunity. This review describes the current status of animal and human vaccine models/studies targeting NoV and addresses the factors hampering the development of a broadly effective vaccine.

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High Serum Levels of Norovirus Genotype-Specific Blocking Antibodies Correlate With Protection From Infection in Children

Abstract: High preexisting norovirus genotype-specific serum IgG titers and blocking activity in children indicate protection from norovirus infection in a strain-specific manner.

Cited by 79 publications

References 43 publications

Genotype Considerations for Virus-Like Particle-Based Bivalent Norovirus Vaccine Composition

Genotype Considerations for Virus-Like Particle-Based Bivalent Norovirus Vaccine Composition

Elevated Serum anti-Helicobacter pylori IgG Levels is a Predictor of Successful Eradication Therapy

Norovirus vaccines: Correlates of protection, challenges and limitations

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