Recalling the #Future: #Immunological #Memory Toward Unpredictable #Influenza Viruses (Front Immunol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Immunol. 2019 Jul 2;10:1400. doi: 10.3389/fimmu.2019.01400. eCollection 2019.

Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses.

Auladell M1, Jia X1, Hensen L1, Chua B1,2, Fox A3, Nguyen THO1, Doherty PC1,4, Kedzierska K1.

Author information: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia. 2 Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan. 3 WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. 4 Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, United States.

 

Abstract

Persistent and durable immunological memory forms the basis of any successful vaccination protocol. Generation of pre-existing memory B cell and T cell pools is thus the key for maintaining protective immunity to seasonal, pandemic and avian influenza viruses. Long-lived antibody secreting cells (ASCs) are responsible for maintaining antibody levels in peripheral blood. Generated with CD4+ T help after naïve B cell precursors encounter their cognate antigen, the linked processes of differentiation (including Ig class switching) and proliferation also give rise to memory B cells, which then can change rapidly to ASC status after subsequent influenza encounters. Given that influenza viruses evolve rapidly as a consequence of antibody-driven mutational change (antigenic drift), the current influenza vaccines need to be reformulated frequently and annual vaccination is recommended. Without that process of regular renewal, they provide little protection against “drifted” (particularly H3N2) variants and are mainly ineffective when a novel pandemic (2009 A/H1N1 “swine” flu) strain suddenly emerges. Such limitation of antibody-mediated protection might be circumvented, at least in part, by adding a novel vaccine component that promotes cross-reactive CD8+ T cells specific for conserved viral peptides, presented by widely distributed HLA types. Such “memory” cytotoxic T lymphocytes (CTLs) can rapidly be recalled to CTL effector status. Here, we review how B cells and follicular T cells are elicited following influenza vaccination and how they survive into a long-term memory. We describe how CD8+ CTL memory is established following influenza virus infection, and how a robust CTL recall response can lead to more rapid virus elimination by destroying virus-infected cells, and recovery. Exploiting long-term, cross-reactive CTL against the continuously evolving and unpredictable influenza viruses provides a possible mechanism for preventing a disastrous pandemic comparable to the 1918-1919 H1N1 “Spanish flu,” which killed more than 50 million people worldwide.

KEYWORDS: B cells; T cells; immunological memory; influenza; vaccine

PMID: 31312199 PMCID: PMC6614380 DOI: 10.3389/fimmu.2019.01400

Keywords: Influenza A; Seasonal Influenza; Pandemic Influenza; Vaccines; Immunology.

——

Advertisements

#Immunogenicity, Lot #Consistency, and Extended #Safety of rVSVΔG-ZEBOV-GP [#Ebola] #Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults

Scott A Halperin, Rituparna Das, Matthew T Onorato, Kenneth Liu, Jason Martin, Rebecca J Grant-Klein, Rick Nichols, Beth-Ann Coller, Frans A Helmond, Jakub K Simon, V920-012 Study Team

The Journal of Infectious Diseases, jiz241, https://doi.org/10.1093/infdis/jiz241

Published: 18 July 2019

 

Abstract

Background

This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).

Methods

Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed.

Results

ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination.

Conclusions

Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development.

Clinical Trials RegistrationNCT02503202.

Ebola, clinical trial, immunogenicity, rVSVΔG-ZEBOV-GP, vaccine

Issue Section: Major Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Ebola; Vaccines.

——-

#Neuraminidase expressing #VLP #vaccine provides effective cross #protection against #influenza virus (Virology, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virology. 2019 Jul 8;535:179-188. doi: 10.1016/j.virol.2019.07.008. [Epub ahead of print]

Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus.

Kim KH1, Lee YT1, Park S1, Jung YJ1, Lee Y1, Ko EJ1, Kim YJ1, Li X2, Kang SM3.

Author information: 1 Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, USA. 2 Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFP, Health Canada, Ottawa, ON, Canada. 3 Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, USA. Electronic address: skang24@gsu.edu.

 

Abstract

Neuraminidase is the second major surface antigen on influenza virus. We investigated the immunogenicity and cross protective efficacy of virus-like particle containing neuraminidase derived from 2009 pandemic H1N1 influenza virus (N1 VLP) in comparison with inactivated split influenza vaccine. Immunization of mice with N1 VLP induced antibody responses specific for virus and cross-reactive neuraminidase inhibition activity whereas an inactivated split vaccine induced strain-specific hemagglutination inhibition activity. N1 VLP-immunized mice developed cross protective immunity against antigenically different influenza viruses, as determined by body weight changes, lung viral titers, infiltrating innate immune cells, and cytokines, and antibody secreting cells, and germinal center B cells. Also, N1 VLP-immune sera provided cross-protection in naïve mice. Immunity by N1 VLP vaccination was not compromised in Fc receptor γ-chain deficient mice. These results suggest that neuraminidase-presenting VLP can be developed as an effective cross-protective vaccine candidate along with current influenza vaccination.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

KEYWORDS: Cross protection; Influenza virus; Neuraminidase vaccine; Virus-like particle

PMID: 31310875 DOI: 10.1016/j.virol.2019.07.008

Keywords: Seasonal Influenza; Vaccines.

——

#Progress in Elucidating Potential #Markers and Mechanisms of Rapid #Protection Conferred by the #VSV-Vectored #Ebola Virus #Vaccine (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Progress in Elucidating Potential Markers and Mechanisms of Rapid Protection Conferred by the VSV-Vectored Ebola Virus Vaccine

Gary Wong

DOI: 10.1128/mBio.01597-19

 

ABSTRACT

Research progress over the past 20 years has yielded several experimental Ebola virus (EBOV) vaccine candidates, which were shown to be effective in nonhuman primates when given 28 days before a lethal challenge. Of these, the vesicular stomatitis virus (VSV)-vectored vaccine against EBOV (VSV-EBOV) is unique at being able to induce rapid protection, with 100% survival achieved as soon as 7 days after EBOV challenge. In a recent mBio article, Menicucci et al. carried out a transcriptome analysis of host responses in monkeys immunized with VSV-EBOV from 28 to 3 days before challenge (A. R. Menicucci, A. Jankeel, H. Feldmann, A. Marzi, and I. Messaoudi, mBio 10:e00597-19, 2019, https://doi.org/10.1128/mBio.00597-19). It was found that surviving animals had a controlled innate immune response coupled with rapid adaptive immunity, but this was not detected in nonsurviving animals. These studies highlight the important role innate immunity plays in creating an antiviral state to restrict EBOV replication and ensuring enough time for the vaccine to induce an effective adaptive immune response.

The views expressed in this article do not necessarily reflect the views of the journal or of ASM.

Keywords: Ebola; Vaccines.

——

#Health #outcomes of young #children born to #mothers who received 2009 #pandemic #H1N1 #influenza #vaccination during #pregnancy: retrospective cohort study (BMJ, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMJ. 2019 Jul 10;366:l4151. doi: 10.1136/bmj.l4151.

Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study.

Walsh LK1,2, Donelle J3, Dodds L4, Hawken S2,3,5, Wilson K2,3,5, Benchimol EI2,3,6, Chakraborty P2,6, Guttmann A3,7,8, Kwong JC3,7,9,10, MacDonald NE4, Ortiz JR11, Sprague AE1,2,6, Top KA4, Walker MC1,2,5, Wen SW2,5, Fell DB12,3,6.

Author information: 1 Better Outcomes Registry & Network, Ottawa, ON, Canada. 2 University of Ottawa, Ottawa, ON, Canada. 3 ICES, Toronto, ON, Canada. 4 Dalhousie University, Halifax, NS, Canada. 5 Ottawa Hospital Research Institute, Ottawa, ON, Canada. 6 Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada. 7 Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 8 Hospital for Sick Children, Toronto, ON, Canada. 9 Public Health Ontario, Toronto, ON, Canada. 10 Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada. 11 University of Maryland School of Medicine, Baltimore, MD, USA. 12 University of Ottawa, Ottawa, ON, Canada dfell@cheo.on.ca.

 

Abstract

OBJECTIVE:

To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood.

DESIGN:

Retrospective cohort study.

SETTING:

Population based birth registry linked with health administrative databases in the province of Ontario, Canada.

PARTICIPANTS:

All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes.

MAIN OUTCOME MEASURES:

Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding.

RESULTS:

Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups.

CONCLUSIONS:

No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PMID: 31292120 DOI: 10.1136/bmj.l4151

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.

——

#Effectiveness of partial and full #influenza #vaccination in #children aged <9 years in #HK, 2011-2019 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Effectiveness of partial and full influenza vaccination in children aged <9 years in Hong Kong, 2011-2019

Huiying Chua, Susan S Chiu, Eunice L Y Chan, Shuo Feng, Mike Y W Kwan, Joshua S C Wong, J S Malik Peiris, Benjamin J Cowling

The Journal of Infectious Diseases, jiz361, https://doi.org/10.1093/infdis/jiz361

Published: 09 July 2019

 

Abstract

INTRODUCTION

Two doses of influenza vaccination are recommended for previously unvaccinated children aged <9 years, and receipt of one dose is sometimes termed “partial vaccination”. We assessed the vaccine effectiveness (VE) against influenza hospitalization of partial and full influenza vaccination among children in Hong Kong.

METHODS

Using the test-negative design we enrolled 23,187 children aged <9 years admitted to hospitals with acute respiratory illness between September 2011 through to March 2019. Vaccination and influenza status were recorded. Fully vaccinated children included those vaccinated with two doses, or one dose if they were previously vaccinated. Partially vaccinated children included those who should receive two doses but received only one dose. We estimated VE using conditional logistic regression models matching on epidemiological week.

RESULTS

Overall VE estimates among fully and partially vaccinated children were 73% (95% confidence interval, CI: 69% ,77%) and 31% (95% CI: 8%, 48%), respectively. Consistently higher VE was observed in fully vaccinated children against each influenza type/subtype. VE of partial vaccination did not vary by age groups.

CONCLUSIONS

Partial vaccination was significantly less effective than full vaccination. Our study supports the current recommendation of two doses of influenza vaccination in previously unvaccinated children <9 years of age.

Topic: influenza – child – hong kong – influenza vaccines – respiratory tract infections – vaccination – vaccines – single-dose regimen

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Seasonal Influenza; Vaccines; HK PRC SAR.

——

Effect of #age on relative #effectiveness of high-dose versus standard-dose #influenza #vaccines among #US #Medicare beneficiaries ages 65 years and older (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Effect of age on relative effectiveness of high-dose versus standard-dose influenza vaccines among US Medicare beneficiaries ages 65 years and older

Yun Lu, PhD, Yoganand Chillarige, MPA, Hector S Izurieta, MD, Yuqin Wei, MS, Wenjie Xu, BA, Michael Lu, BS, Heng-Ming Sung, MPH, Arnstein Lindaas, MA, Michael Wernecke, BS, Thomas MaCurdy, PhD, Jeffrey Kelman, MD, Richard A Forshee, PhD

The Journal of Infectious Diseases, jiz360, https://doi.org/10.1093/infdis/jiz360

Published: 09 July 2019

 

Abstract

Background

Studies have found that the high-dose influenza vaccine has higher relative vaccine effectiveness (RVE) compared to standard-dose vaccines in some seasons. We evaluated the effect of age on the high-dose versus standard-dose RVE among Medicare beneficiaries.

Methods

A six-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries ages ≥65 years. Poisson regression was used to evaluate the effect of age on high-dose versus standard-dose RVE in preventing influenza hospitalizations.

Results

The study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza hospital encounters (influenza inpatient stays and emergency department visits) in the 2012–13 (RVE 23.1%, 95% CI 17.6–28.3%), 201314 (RVE 15.3%, 95% CI 7.8–22.3%), 201415 (RVE 8.9%, 95% CI 5.6–12.1%), and 201617 (RVE 12.6%, 95% CI 6.3–18.4%) seasons, and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines for people ages ≥85 years across all seasons. Similar trends were observed for influenza inpatient stays.

Conclusions

The high-dose versus standard-dose influenza vaccine RVE increases with age.

influenza vaccine, relative vaccine effectiveness, high-dose vaccine, effect of age, Medicare

Topic:  influenza – influenza vaccines – inpatients – medicare – vaccines

Issue Section: Major Article

This content is only available as a PDF.

Published by Oxford University Press for the Infectious Diseases Society of America 2019.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Seasonal Influenza; Vaccines; USA.

——