#Medical #Outcomes in Women Who Became #Pregnant after #Vaccination with a #VLP Experimental #Vaccine against #Influenza A (#H1N1) 2009 Virus Tested during 2009 #Pandemic Outbreak (Viruses, abstract)

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

Viruses. 2019 Sep 17;11(9). pii: E868. doi: 10.3390/v11090868.

Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak.

Cérbulo-Vázquez A1, Arriaga-Pizano L2, Cruz-Cureño G3, Boscó-Gárate I4, Ferat-Osorio E5, Pastelin-Palacios R6, Figueroa-Damian R7, Castro-Eguiluz D8, Mancilla-Ramirez J9, Isibasi A10, López-Macías C11,12,13.

Author information: 1 Facultad de Medicina, Plan de Estudios Combinados en Medicina (MD, PhD Program), Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico. cerbulo@unam.mx. 2 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. landapi@hotmail.com. 3 Escuela Nacional de Ciencias Biológicas, Programa de Inmunología, Instituto Politécnico Nacional, Mexico City CP 11340, Mexico. gabrielacruz30@gmail.com. 4 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. ibosco45@hotmail.com. 5 Servicio de Cirugía Gastrointestinal, Unidad Médica de Alta Especialidad, Hospital de Especialidades Dr Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. eduardoferat@prodigy.net.mx. 6 Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico. rodolfop@unam.mx. 7 Departamento de Infectología, Instituto Nacional de Perinatología, Mexico City CP 11000, Mexico. rfd6102@yahoo.com.mx. 8 Consejo Nacional de Ciencia y Tecnología (CONACYT)- Departamento de Investigación Clínica, Instituto Nacional de Cancerología, Mexico City CP 14080, Mexico. angeldenisse@gmail.com. 9 Escuela Superior de Medicina, Instituto Politécnico Nacional; Hospital de la Mujer, Secretaria de Sauld, Mexico City CP 11340, Mexico. javiermancilla@hotmail.com. 10 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. isibasi@prodigy.net.mx. 11 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. constantino@sminmunologia.mx. 12 Visiting Professor of Immunology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK. constantino@sminmunologia.mx. 13 Mexican Translational Immunology Research Group, Federation of Clinical Immunology Societies Centers of Excellence, National Autonomous University of Mexico, Mexico City 04510, Mexico. constantino@sminmunologia.mx.



The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 μg dose of VLP vaccine, or (3) 45 μg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants.

KEYWORDS: antibody titers; influenza A(H1N1)pdm09; pregnant women; vaccination; virus-like particle

PMID: 31533277 DOI: 10.3390/v11090868

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.



Long-term #dynamics of #measles in #London: Titrating the impact of #wars, the 1918 #pandemic, and #vaccination (PLoS Comput Biol., abstract)

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

PLoS Comput Biol. 2019 Sep 12;15(9):e1007305. doi: 10.1371/journal.pcbi.1007305. eCollection 2019 Sep.

Long-term dynamics of measles in London: Titrating the impact of wars, the 1918 pandemic, and vaccination.

Becker AD1, Wesolowski A2, Bjørnstad ON3,4, Grenfell BT1,4,5.

Author information: 1 Department of Ecology and Evolutionary Biology, Princeton, New Jersey, United States of America. 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. 3 Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, Pennsylvania, United States of America. 4 Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America. 5 Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, New Jersey, United States of America.



A key question in ecology is the relative impact of internal nonlinear dynamics and external perturbations on the long-term trajectories of natural systems. Measles has been analyzed extensively as a paradigm for consumer-resource dynamics due to the oscillatory nature of the host-pathogen life cycle, the abundance of rich data to test theory, and public health relevance. The dynamics of measles in London, in particular, has acted as a prototypical test bed for such analysis using incidence data from the pre-vaccination era (1944-1967). However, during this timeframe there were few external large-scale perturbations, limiting an assessment of the relative impact of internal and extra demographic perturbations to the host population. Here, we extended the previous London analyses to include nearly a century of data that also contains four major demographic changes: the First and Second World Wars, the 1918 influenza pandemic, and the start of a measles mass vaccination program. By combining mortality and incidence data using particle filtering methods, we show that a simple stochastic epidemic model, with minimal historical specifications, can capture the nearly 100 years of dynamics including changes caused by each of the major perturbations. We show that the majority of dynamic changes are explainable by the internal nonlinear dynamics of the system, tuned by demographic changes. In addition, the 1918 influenza pandemic and World War II acted as extra perturbations to this basic epidemic oscillator. Our analysis underlines that long-term ecological and epidemiological dynamics can follow very simple rules, even in a non-stationary population subject to significant perturbations and major secular changes.

PMID: 31513578 DOI: 10.1371/journal.pcbi.1007305

Keywords: Pandemic Influenza; Spanish Flu; Wars; Society; Measles.


Better Prepare Than React: Reordering #PublicHealth #Priorities 100 Years After the #SpanishFlu #Epidemic (Am J Public Health, abstract)

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

Am J Public Health. 2018 Nov;108(11):1465-1468. doi: 10.2105/AJPH.2018.304682. Epub 2018 Sep 25.

Better Prepare Than React: Reordering Public Health Priorities 100 Years After the Spanish Flu Epidemic.

Greenberger M1.

Author information: 1 Michael Greenberger is with the Carey School of Law and the Center for Health and Homeland Security, University of Maryland, Baltimore. He is also the founder and director of the University of Maryland Center for Health and Homeland Security.



This commentary argues that 100 years after the deadly Spanish flu, the public health emergency community’s responses to much more limited pandemics and outbreaks demonstrate a critical shortage of personnel and resources. Rather than relying on nonpharmaceutical interventions, such as quarantine, the United States must reorder its health priorities to ensure adequate preparation for a large-scale pandemic.

PMID: 30252520 PMCID: PMC6187800 DOI: 10.2105/AJPH.2018.304682 [Indexed for MEDLINE] Free PMC Article

Keywords: Pandemic Influenza; Pandemic Preparedness; Spanish Flu; USA.


The #SpanishFlu, #Epidemics, and the Turn to #Biomedical #Responses (Am J Public Health, abstract)

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

Am J Public Health. 2018 Nov;108(11):1455-1458. doi: 10.2105/AJPH.2018.304581. Epub 2018 Sep 25.

The Spanish Flu, Epidemics, and the Turn to Biomedical Responses.

Schwartz JL1.

Author information: 1 The author is with the Department of Health Policy and Management, Yale School of Public Health, and Section of the History of Medicine, Yale School of Medicine, New Haven, CT.



A century ago, nonpharmaceutical interventions such as school closings, restrictions on large gatherings, and isolation and quarantine were the centerpiece of the response to the Spanish Flu. Yet, even though its cause was unknown and the science of vaccine development was in its infancy, considerable enthusiasm also existed for using vaccines to prevent its spread. This desire far exceeded the scientific knowledge and technological capabilities of the time. Beginning in the early 1930s, however, advances in virology and influenza vaccine development reshaped the relative priority given to biomedical approaches in epidemic response over traditional public health activities. Today, the large-scale implementation of nonpharmaceutical interventions akin to the response to the Spanish Flu would face enormous legal, ethical, and political challenges, but the enthusiasm for vaccines and other biomedical interventions that was emerging in 1918 has flourished. The Spanish Flu functioned as an inflection point in the history of epidemic responses, a critical moment in the long transition from approaches dominated by traditional public health activities to those in which biomedical interventions are viewed as the most potent and promising tools in the epidemic response arsenal.

PMID: 30252511 DOI: 10.2105/AJPH.2018.304581 [Indexed for MEDLINE]

Keywords: Pandemic Influenza; Pandemic Preparedness; Spanish Flu; Infectious diseases; Vaccines; Quarantine measures.


The #PanVax #Tool to Improve #Pandemic #Influenza #Emergency #Vaccination Program #Readiness and Partnership (Am J Public Health, abstract)

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

Am J Public Health. 2019 Sep;109(S4):S322-S324. doi: 10.2105/AJPH.2019.305233.

The PanVax Tool to Improve Pandemic Influenza Emergency Vaccination Program Readiness and Partnership.

Carias C1, Lehnert JD1, Greening B Jr1, Adhikari BB1, Kahn EB1, Meltzer MI1, Graitcer SB1.

Author information: 1 Cristina Carias, Bradford Greening Jr, Emily B. Kahn, and Martin I. Meltzer are with the Health Economics and Modeling Unit, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA. Jonathan D. Lehnert, Bishwa B. Adhikari, and Samuel B. Graitcer are with the Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention. Jonathan D. Lehnert is also with IHRC, Atlanta.




To show how the Centers for Disease Control and Prevention’s Pandemic Vaccine Campaign Planning Tool (PanVax Tool) can help state and local public health emergency planners demonstrate and quantify how partnerships with community vaccine providers can improve their overall pandemic vaccination program readiness.


The PanVax Tool helps planners compare different strategies to vaccinate their jurisdiction’s population in a severe pandemic by allowing users to customize the underlying model inputs in real time, including their jurisdiction’s size, community vaccine provider types, and how they allocate vaccine to these providers. In this report, we used a case study with hypothetical data to illustrate how jurisdictions can utilize the PanVax Tool for preparedness planning.


By using the tool, planners are able to understand the impact of engaging with different vaccine providers in a vaccination campaign.


The PanVax Tool is a useful tool to help demonstrate the impact of community vaccine provider partnerships on pandemic vaccination readiness and identify areas for improved partnerships for pandemic response.

PMID: 31505153 DOI: 10.2105/AJPH.2019.305233

Keywords: Pandemic Influenza; Vaccines; Pandemic Preparedness; USA.


#Evaluation of novel #disposable #bioreactors on #pandemic #influenza virus production [#CVV] (PLoS One, abstract)

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


Evaluation of novel disposable bioreactors on pandemic influenza virus production

Chia-Chun Lai, Tsai-Chuan Weng, Yu-Fen Tseng, Jen-Ron Chiang, Min-Shi Lee, Alan Yung-Chih Hu

Published: August 12, 2019 / DOI: https://doi.org/10.1371/journal.pone.0220803



Since 1997, the highly pathogenic influenza H5N1 virus has spread from Hong Kong. According to the WHO bulletin report, the H5N1 virus is a zoonotic disease threat that has infected more than 850 humans, causing over 450 deaths. In addition, an outbreak of another new and highly pathogenic influenza virus (H7N9) occurred in 2013 in China. These highly pathogenic influenza viruses could potentially cause a worldwide pandemic. it is crucial to develop a rapid production platform to meet this surge demand against any possible influenza pandemic. A potential solution for this problem is the use of cell-based bioreactors for rapid vaccine production. These novel bioreactors, used for cell-based vaccine production, possess various advantages. For example, they enable a short production time, allow for the handling highly pathogenic influenza in closed environments, and can be easily scaled up. In this study, two novel disposable cell-based bioreactors, BelloCell and TideCell, were used to produce H5N1 clade II and H7N9 candidate vaccine viruses (CVVs). Madin-Darby canine kidney (MDCK) cells were used for the production of these influenza CVVs. A novel bench-scale bioreactor named BelloCell bioreactor was used in the study. All culturing conditions were tested and scaled to 10 L industrial-scale bioreactor known as TideCell002. The performances of between BelloCell and TideCell were similar in cell growth, the average MDCK cell doubling time was slightly decreased to 25 hours. The systems yielded approximately 39.2 and 18.0 μg/ml of HA protein with the 10-liter TideCell002 from the H5N1 clade II and H7N9 CVVs, respectively. The results of this study not only highlight the overall effectiveness of these bioreactors but also illustrate the potential of maintaining the same outcome when scaled up to industrial production, which has many implications for faster vaccine production. Although additional studies are required for process optimization, the results of this study are promising and show that oscillating bioreactors may be a suitable platform for pandemic influenza virus production.


Citation: Lai C-C, Weng T-C, Tseng Y-F, Chiang J-R, Lee M-S, Hu AY-C (2019) Evaluation of novel disposable bioreactors on pandemic influenza virus production. PLoS ONE 14(8): e0220803. https://doi.org/10.1371/journal.pone.0220803

Editor: Balaji Manicassamy, University of Iowa, UNITED STATES

Received: February 20, 2019; Accepted: July 23, 2019; Published: August 12, 2019

Copyright: © 2019 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: The authors would like to thank Mr. Anthony Chang for English editing, and the US CDC for supplying the egg-derived vaccine strains. The authors would also like to thank the funding support from the Ministry of Science and Technology (R.O.C. 102-2622-B-400-001-CC2; 103-2622-B-400-001-CC2). Mr. Chia-Chun Lai is currently pursuing his Ph.D. studies under the Graduate Program of Biotechnology in Medicine, National Tsing Hua University and the National Health Research Institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Avian Influenza; H5N1; H7N9; Vaccines; Pandemic preparedness.


Safety and immunogenicity of unadjuvanted subvirion #monovalent inactivated #influenza #H3N2 variant (#H3N2v) #vaccine in #children and #adolescents (Vaccine, abstract)

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

Vaccine. 2019 Jul 30. pii: S0264-410X(19)31006-0. doi: 10.1016/j.vaccine.2019.07.085. [Epub ahead of print]

Safety and immunogenicity of unadjuvanted subvirion monovalent inactivated influenza H3N2 variant (H3N2v) vaccine in children and adolescents.

Munoz FM1, Anderson EJ2, Bernstein DI3, Harrison CJ4, Pahud B4, Anderson E5, Creech CB6, Berry AA7, Kotloff KL7, Walter EB8, Atmar RL9, Bellamy AR10, Chang S11, Keitel WA9.

Author information: 1 Departments of Pediatrics, Baylor College of Medicine, Houston, TX, United States; Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States. Electronic address: florm@bcm.edu. 2 Department of Pediatrics and Medicine, Emory University School of Medicine, Atlanta, GA, United States. 3 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States. 4 Department of Pediatrics, Children’s Mercy Hospital Kansas City, Kansas City, MO, United States. 5 Department of Pediatrics, Saint Louis University School of Medicine, St. Louis, MO, United States. 6 Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States. 7 Department of Pediatrics and Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States. 8 Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States. 9 Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States; Medicine, Baylor College of Medicine, Houston, TX, United States. 10 The Emmes Corporation, Rockville, MD, United States. 11 National Institute of Allergy and Infectious Diseases, Rockville, MD, United States.




In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children.


This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6-35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3-17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated.


The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6-35 months, and headache and fatigue in children 9-17 years old. Children 6-35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9-17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9-17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses.


The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Adolescents; Children; Cross-reactive antibodies; H3N2 variant; Immunogenicity; Influenza; Safety

PMID: 31375440 DOI: 10.1016/j.vaccine.2019.07.085

Keywords: Swine Influenza; Influenza A; Seasonal Influenza; Pandemic Influenza; H3N2v; Pediatrics; Vaccines.