#Compressed #Influenza #Vaccination in #US Older Adults: A Decision Analysis (Am J Prev Med., abstract)

[Source: American Journal of Preventive Medicine, full page: (LINK). Abstract, edited.]

Compressed Influenza Vaccination in U.S. Older Adults: A Decision Analysis

Kenneth J. Smith, MD, MS, Glenson France, MA, Mary Patricia Nowalk, PhD, Jonathan M. Raviotta, MPH, Jay DePasse, BS, Angela Wateska, MPH, Eunha Shim, PhD, Richard K. Zimmerman, MD, MPH

DOI: https://doi.org/10.1016/j.amepre.2018.11.015

Published online: February 14, 2019




Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April.


A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August–May) to maximize vaccine uptake or (2) vaccination compressed to October–May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%–11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018.


Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored.


Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season.

© 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Keywords: Seasonal Influenza; Vaccines; USA.



Principal #Controversies in #Vaccine #Safety in the #USA (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2019 Feb 12. doi: 10.1093/cid/ciz135. [Epub ahead of print]

Principal Controversies in Vaccine Safety in the United States.

DeStefano F1, Bodenstab HM2, Offit PA3.

Author information: 1 Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA. 2 Department of Pharmacy Services, The Children’s Hospital of Philadelphia, Philadelphia, PA. 3 Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA.



Concerns about vaccine safety can lead to decreased acceptance of vaccines and resurgence of vaccine-preventable diseases. We summarize the key evidence on some of the main current vaccine safety controversies in the United States, including: 1) MMR vaccine and autism; 2) thimerosal, a mercury-based vaccine preservative, and the risk of neurodevelopmental disorders; 3) vaccine-induced Guillain-Barré Syndrome (GBS); 4) vaccine-induced autoimmune diseases; 5) safety of HPV vaccine; 6) aluminum adjuvant-induced autoimmune diseases and other disorders; and 7) too many vaccines given early in life predisposing children to health and developmental problems. A possible small increased risk of GBS following influenza vaccination has been identified, but the magnitude of the increase is less than the risk of GBS following influenza infection. Otherwise, the biological and epidemiologic evidence does not support any of the reviewed vaccine safety concerns.

PMID:  30753348  DOI: 10.1093/cid/ciz135

Keywords: Society; Vaccines; USA.


Annual #report on #influenza viruses received and tested by the #Melbourne #WHO CC for #Reference and Research on Influenza in 2016 (Commun Dis Intell (2018), abstract)

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

Commun Dis Intell (2018). 2019 Feb 1;43. doi: 10.33321/cdi.2019.43.5.

Annual report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2016

Leung VK1, Deng YM1, Kaye M1, Leang SK1, Gillespie L1, Chow MK1.

Author information: 1 WHO Collaborating Centre for Reference and Research on Influenza



As part of its role in the World Health Organization’s (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 4,247 human influenza positive samples during 2016. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties and also propagated in qualified cells and hens eggs for potential seasonal influenza vaccine virus candidates. In 2016, influenza A(H3) viruses predominated over influenza A(H1)pdm09 and B viruses, accounting for a total of 51% of all viruses analysed. The vast majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2016. However, phylogenetic analysis of a selection of viruses indicated that the majority of circulating A(H3) viruses had undergone some genetic drift relative to the WHO recommended strain for 2016. Of more than 3,000 samples tested for resistance to the neuraminidase inhibitors oseltamivir and zanamivir, six A(H1)pdm09 viruses and two B/Victoria lineage viruses showed highly reduced inhibition to oseltamivir.

© Commonwealth of Australia CC BY-NC-ND

PMID: 30739429

Keywords: Seasonal Influenza; Vaccines; Antivirals; Drugs Resistance; Australia.


#Antibody #kinetics following #vaccination with #MenAfriVac: an analysis of serological data from randomised trials (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Antibody kinetics following vaccination with MenAfriVac: an analysis of serological data from randomised trials

Michael White, PhD, Olubukola Idoko, MD, Samba Sow, MD, Aldiouma Diallo, PhD, Beate Kampmann, PhD, Ray Borrow, PhD, Caroline Trotter, PhD

Published: February 08, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30674-1




A meningococcal group A conjugate vaccine, PsA-TT (also known as MenAfriVac), was developed with the support of the Meningitis Vaccine Project. Around 280 million individuals aged 1–29 years have been immunised across the African meningitis belt. We analysed the kinetics of vaccine-induced antibody response and assessed the possible implications for duration of protection.


We obtained data from two longitudinal studies done in The Gambia, Mali, and Senegal of antibody responses in 193 children aged 12–23 months and 604 participants aged 2–29 years following MenAfriVac vaccination. Antibodies were measured using two methods: group A serum bactericidal antibody (SBA) assay and group A-specific IgG ELISA. Data on antibody responses were analysed using a mixed-effects statistical model accounting for the mean response and variation in patterns of antibody kinetics. Determinants of antibody duration were investigated using regression analysis.


In children age 12–23 months, the reduction in MenAfriVac-induced antibody levels assessed by SBA titres had two phases: with 97·0% (95% credible interval [CrI] 95·1–98·3) of the response being short lived and decaying within the first 6 months and the remainder being long lived and decaying with a half-life of 2690 days (95% CrI 1016–15 078). Antibody levels assessed by SBA titres in participants aged 2–29 years were more persistent, with 95·0% (85·7–98·1) of the response being short lived, and the long lived phase decaying with a half-life of 6007 days (95% CrI 2826–14 279). Greater pre-vaccination antibody levels were associated with greater immunogenicity following vaccination, as well as greater antibody persistence. Despite rapid antibody declines in the first phase, antibodies in the second phase persisted at SBA titres greater than 128. Although there is no strong evidence base for a correlate of protection against infection with Neisseria meningitidis serogroup A, we use an assumed SBA titre of 128 as a threshold of protection to predict that 20 years after vaccination with a single dose of MenAfriVac, vaccine efficacy will be 52% (29–73) in children vaccinated at age 12–23 months and 70% (60–79) in participants vaccinated at age 2–29 years.


Population-level immunity induced by routine vaccination with the Expanded Programme on Immunization is predicted to persist at levels sufficient to confer more than 50% protection over a 20-year time period. Further increases in population-level immunity could be obtained via mass campaigns or by delaying the age of vaccination through the Expanded Programme on Immunization. However, the benefits of such a strategy would need to be weighed against the risks of leaving young children unvaccinated for longer.


Meningitis Vaccine Project and Institut Pasteur.

Keywords: Neisseria meningitidis sg A; Vaccines; African Region.


A recombinant #VSV-based #Lassa fever #vaccine elicits rapid and long-term protection from lethal Lassa virus #infection in guinea pigs (npj Vaccines, abstract)

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

Article | OPEN | Published: 08 February 2019

A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs

Derek R. Stein, Bryce M. Warner, Geoff Soule, Kevin Tierney, Kathy L. Frost, Stephanie Booth & David Safronetz

npj Vaccines, volume 4, Article number: 8 (2019)



The World Health Organization has identified Lassa virus (LASV) as one of the top five pathogens to cause a severe outbreak in the near future. This study assesses the ability of a leading vaccine candidate, recombinant Vesicular stomatitis virus expressing LASV glycoprotein (VSVΔG/LASVGPC), and its ability to induce rapid and long-term immunity to lethal guinea pig-adapted LASV (GPA-LASV). Outbred guinea pigs were vaccinated with a single dose of VSVΔG/LASVGPC followed by a lethal challenge of GPA-LASV at 7, 14, 25, 189, and 355 days post-vaccination. Statistically significant rapid and long-term protection was achieved at all time points with 100% protection at days 7 and 14 post-vaccination. While 83 and 87% protection were achieved at 25 days and 6 months post-vaccination, respectively. When guinea pigs were challenged one year after vaccination 71% protection was achieved. Notable infectious virus was isolated from the serum and tissues of some but not all animals. Total LASVGPC-specific IgG titers were also measured on a monthly basis leading up to LASV challenge however, it is unclear if antibody alone correlates with short and long term survival. These studies confirm that a single dose of VSVΔG/LASVGPC can induce rapid and long-term protection from LASV infection in an aggressive outbred model of infection, and supports further development in non-human primates.

Keywords: Lassa fever; Vaccines; Animal models.


Evaluating Promising #Investigational #Medical #Countermeasures: #Recommendations in the Absence of #Guidelines (Health Secur., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Health Secur. 2019 Feb 6. doi: 10.1089/hs.2018.0092. [Epub ahead of print]

Evaluating Promising Investigational Medical Countermeasures: Recommendations in the Absence of Guidelines.

Bhadelia N1, Sauer L2, Cieslak TJ3, Davey RT4, McLellan S5, Uyeki TM6, Kortepeter MG7; National Ebola Training and Education Center’s Special Pathogens Research Network (SPRN)’s Medical Countermeasures Working Group.

Collaborators (12): Akers M, Dierberg K, Eiras D, Evans J, Figueroa E, Kraft C, Kratochvil C, Martins K, Measer G, Mehta A, Hu-Primmer J, Risi G.

Author information: 1 Nahid Bhadelia, MD, MA, is Medical Director, Special Pathogens Unit, Section of Infectious Diseases, Boston University School of Medicine, Boston, MA. 2 Lauren Sauer, MS, is Assistant Professor, Director of Research, Johns Hopkins Biocontainment Unit, Department of Emergency Medicine, Johns Hopkins Medicine, Baltimore, MD. 3 Theodore J. Cieslak, MD, MPH, is Associate Professor, Department of Epidemiology, University of Nebraska College of Public Health, Omaha, NE. 4 Richard T. Davey, MD, is Deputy Clinical Director, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD. 5 Susan McLellan, MD, MPH, is Medical Director, Biocontainment Treatment Unit, Division of Infectious Diseases, University of Texas Medical Branch at Galveston, TX. 6 Timothy M. Uyeki, MD, MPH, MPP, is Chief Medical Officer, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA. 7 Mark G. Kortepeter, MD, MPH, is Professor, Department of Epidemiology, University of Nebraska College of Public Health, Omaha, NE.



Emerging and re-emerging infectious diseases pose growing global public health threats. However, research on and development of medical countermeasures (MCMs) for such pathogens is limited by the sporadic and unpredictable nature of outbreaks, lack of financial incentive for pharmaceutical companies to develop interventions for many of the diseases, lack of clinical research capacity in areas where these diseases are endemic, and the ethical dilemmas related to conducting scientific research in humanitarian emergencies. Hence, clinicians providing care for patients with emerging diseases are often faced with making clinical decisions about the safety and effectiveness of experimental MCMs, based on limited or no human safety, preclinical, or even earlier product research or historical data, for compassionate use. Such decisions can have immense impact on current and subsequent patients, the public health response, and success of future clinical trials. We highlight these dilemmas and underscore the need to proactively set up procedures that allow early and ethical deployment of MCMs as part of clinical trials. When clinical trials remain difficult to deploy, we present several suggestions of how compassionate use of off-label and unlicensed MCMs can be made more informed and ethical. We highlight several collaborations seeking to address these gaps in data and procedures to inform future clinical and public health decision making.

KEYWORDS: Drug development; Ebola; Emerging infectious diseases; Ethics; Medical countermeasures; Outbreaks

PMID: 30724616 DOI: 10.1089/hs.2018.0092

Keywords: Infectious Diseases; Emerging Diseases; Antivirals; Vaccines.


Protective #immunity by an engineered #DNA #vaccine for #Mayaro virus (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Protective immunity by an engineered DNA vaccine for Mayaro virus

Hyeree Choi, Sagar B. Kudchodkar, Emma L. Reuschel, Kanika Asija, Piyush Borole, Michelle Ho, Krzysztof Wojtak, Charles Reed, Stephanie Ramos, Nathen E. Bopp, Patricia V. Aguilar, Scott C. Weaver, J. Joseph Kim,  [ … ], Kar Muthumani


Published: February 7, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007042



Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.


Author summary

Mayaro virus (MAYV) is a mosquito-transmitted virus that causes fever, headache, chills, nausea and joint pain that can last for months after infection. The rising number of cases, due to increased mosquito circulation, and the threat of an epidemic emphasize its importance as an emerging virus, but there are no licensed vaccines to prevent Mayaro infection nor therapeutics to treat it. In this study, we gathered fundamental knowledge on how the immune system responds to MAYV infection, and we evaluated the efficacy of a novel, synthetic DNA envelope vaccine (scMAYV-E) in mice. Analysis of immune responses in mice demonstrated that this vaccine induces potent T cell immunity and antibodies. Mice who receive the vaccine and then are challenged with live MAYV are protected against Mayaro disease. This data provides evidence that the DNA-based MAYV vaccine may be able to prevent Mayaro disease. Thus, the scMAYV-E vaccine is a promising step forward for MAYV vaccine development. Future testing will evaluate whether this vaccine is a viable means to halt the spread of MAYV and protect individuals from Mayaro disease.


Citation: Choi H, Kudchodkar SB, Reuschel EL, Asija K, Borole P, Ho M, et al. (2019) Protective immunity by an engineered DNA vaccine for Mayaro virus. PLoS Negl Trop Dis 13(2): e0007042. https://doi.org/10.1371/journal.pntd.0007042

Editor: Kenneth E. Olson, Colorado State University, UNITED STATES

Received: April 16, 2018; Accepted: November 30, 2018; Published: February 7, 2019

Copyright: © 2019 Choi 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 paper and its Supporting Information files.

Funding: KM and DBW note funding by Inovio Pharmaceuticals, PA, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: CCR, SR, LH, and JJK are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options. KM discloses grant funding, industry collaborations, speaking honoraria, and fees for consulting. He has received consulting fees from Inovio Pharmaceuticals related to DNA vaccine development. He has a patent application for DNA vaccine development and delivery of DNA encoded monoclonal antibodies pending to Inovio Pharmaceuticals. Remuneration includes direct payments. DBW is the W.W. Smith Charitable Trust Professor in Cancer Research at the Wistar Institute. DBW discloses grant funding, SAB and Board service, industry collaborations, speaking honoraria, and fees for consulting. His service includes serving on scientific review committees and advisory boards. Remuneration includes direct payments and/or stock or stock options. He notes potential conflicts associated with this work with Pfizer, Bristol Myers Squibb, Inovio Pharmaceuticals, Merck, VGXI, Geneos, Astrazeneca and potentially others. Licensing of technology from this laboratory has created over 150 jobs in the biotech/pharma industry. The other authors declare no competing financial interests.

Keywords: Alphavirus; Mayaro virus; Vaccines; Animal models.