Boosting #Global #YellowFever #Vaccine #Supply for #Epidemic #Preparedness: 3 Actions for #China and the #USA (Virol Sin., abstract)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Boosting Global Yellow Fever Vaccine Supply for Epidemic Preparedness: 3 Actions for China and the USA

Authors: Daniel R. Lucey, Kristen R. Kent

Perspective / First Online: 24 May 2019


Yellow fever (YF) is an acute disease caused by a flavivirus that infects the liver. It can cause jaundice, bleeding, kidney damage, and death. No antiviral therapy exists. A vaccine does exist, however, and fortunately confers life-long immunity after a single dose (Monath et al.2016; WHO 2017a, b).




Compliance with Ethical Standards

Conflict of interest: The authors declare that they have no conflict of interest.

Animal and Human Rights Statement: This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Yellow Fever; Vaccines; USA; China.



One hundred years after the 1918 #pandemic: new concepts for #preparing for #influenza pandemics (Curr Opin Infect Dis., abstract)

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

Curr Opin Infect Dis. 2019 May 20. doi: 10.1097/QCO.0000000000000564. [Epub ahead of print]

One hundred years after the 1918 pandemic: new concepts for preparing for influenza pandemics.

Pavia A1.

Author information: 1 Division of Pediatric Infectious Diseases, University of Utah, Salt Lake City, Utah, USA.




In the 100 years since the influenza pandemic of 1918-1919, the most deadly event in human history, we have made substantial progress yet we remain vulnerable to influenza pandemics This article provides a brief overview of important advances in preparing for an influenza pandemic, viewed largely from the perspective of the healthcare system.


We have gained insights into influenza pathogenicity, the animal reservoir and have improved global surveillance for new strains and tools for assessing the pandemic risk posed by novel strains. Public health has refined plans for severity assessment, distribution of countermeasures and nonpharmaceutical approaches. Modest improvements in vaccine technology include cell culture-based vaccines, adjuvanted vaccine and recombinant technology. Conventional infection control tools will be critical in healthcare settings. New evidence suggests that influenza virus may be present in aerosols; the contribution of airborne transmission and role of N95 respirators remains unknown. Baloxavir and pimodivir are new antivirals that may improve treatment, especially for severely ill patients. Optimal use and the risk of resistance require further study.


Despite the progress in pandemic preparedness, gaps remain including important scientific questions, adequate resources and most importantly, the ability to rapidly deliver highly effective vaccines.

PMID: 31116135 DOI: 10.1097/QCO.0000000000000564

Keywords: Pandemic Influenza; Spanish flu; Pandemic Preparedness; Antivirals; Vaccines.


Remaining #effect of #influenza #vaccines received in prior #seasons (J Infect Dis., abstract)

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

Remaining effect of influenza vaccines received in prior seasons

Iván Martínez-Baz, Ana Navascués, Itziar Casado, Aitziber Aguinaga, Carmen Ezpeleta, Jesús Castilla

The Journal of Infectious Diseases, jiz266,

Published: 20 May 2019



This study evaluates the remaining effect of influenza vaccines received in the 5 prior seasons. During 7 influenza seasons 8933 patients were enrolled and 47% were confirmed for influenza. As compared to unvaccinated individuals in the current and 5 prior seasons, vaccination was protective when the last dose had been received in the current season (40%; 95%CI, 32-47), and one (42%; 95%CI, 27-54), 2-3 (35%; 95%CI, 16-49) or 4-5 seasons before (31%; 95%CI, 4-51). This effect lasted less in the elderly and chronic patients. On average, several recent prior doses were as protective as current season vaccination.

influenza, influenza vaccine, vaccination history, repeated vaccination, vaccine effectiveness, case-control study, test-negative study

Topic: influenza – influenza vaccines – vaccination – vaccines – elderly

Issue Section: Brief Report

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:

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (

Keywords: Seasonal Influenza; Vaccines.


#Mucosal #Immunity against #Neuraminidase Prevents #Influenza B Virus #Transmission in Guinea Pigs (mBio, abstract)

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

Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

Meagan McMahon, Ericka Kirkpatrick, Daniel Stadlbauer, Shirin Strohmeier, Nicole M. Bouvier, Florian Krammer

Stacey Schultz-Cherry, Editor

DOI: 10.1128/mBio.00560-19



Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses.



Recently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.

Keywords: Seasonal Influenza; Influenza B; Vaccines; Animal models.


Sequential #Immunization With Live-Attenuated Chimeric #Hemagglutinin-Based Vaccines Confers #Heterosubtypic Immunity Against #Influenza A Viruses in a Preclinical Ferret Model (Front Immunol., abstract)

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

Front Immunol. 2019 Apr 10;10:756. doi: 10.3389/fimmu.2019.00756. eCollection 2019.

Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model.

Liu WC1,2, Nachbagauer R1, Stadlbauer D1, Solórzano A1, Berlanda-Scorza F3, García-Sastre A1,2,4, Palese P1,4, Krammer F1, Albrecht RA1,2.

Author information: 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 2 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 3 PATH US, Seattle, WA, United States. 4 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.



Due to continuous antigenic drift and occasional antigenic shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with “exotic” head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4+IFN-γ+ and CD8+IFN-γ+ effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here.

KEYWORDS: chimeric hemagglutinin; ferret; heterosubtypic protection; live-attenuated influenza vaccine; stalk antibody; universal influenza virus vaccine

PMID: 31105689 PMCID: PMC6499175 DOI: 10.3389/fimmu.2019.00756

Keywords: Influenza A; Vaccines; Animal models.


#Risk modeling the #mortality impact of #antimicrobial #resistance in secondary #pneumococcal #pneumonia infections during the 2009 #influenza #pandemic (Int J Infect Dis., abstract)

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

Int J Infect Dis. 2019 May 13. pii: S1201-9712(19)30211-5. doi: 10.1016/j.ijid.2019.05.005. [Epub ahead of print]

Risk modeling the mortality impact of antimicrobial resistance in secondary pneumococcal pneumonia infections during the 2009 influenza pandemic.

Barnes CE1, MacIntyre CR2.

Author information: 1 School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia. Electronic address: 2 School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia; The Kirby Institute, Sydney, Australia. Electronic address:




The aim of this study was to estimate the impact of antimicrobial resistance (AMR) in secondary pneumococcal pneumonia infections on global mortality during the 2009 influenza pandemic, to estimate future pandemic mortality risk and to inform pandemic preparedness.


Risk analysis modeling was conducted using a multivariate risk formula. Literature reviews were conducted to generate global central estimates for each of the parameters of the risk formula in relation to the 2009 influenza pandemic, secondary pneumococcal pneumonia, rates of AMR and pneumococcal vaccine efficacy as a component of pandemic preparedness.


Global Streptococcus pneumoniae AMR was estimated at 21.8% to 27.6%, and contributed to 1.8% to 2.3% of deaths during the 2009 influenza pandemic. When directly applied to mortality due to multidrug resistance, pneumococcal vaccination could potentially prevent 1,277 to 3,754 deaths and could have reduced mortality from multidrug resistant S. pneumoniae to 1% to 1.2%.


AMR in secondary pneumococcal infections contributed towards a small percentage of the global mortality during the 2009 influenza pandemic. Increased S. pnuemoniae AMR could result in a three- to four-fold rise in mortality due to secondary pneumococcal infections in future influenza pandemics. Pneumococcal vaccination has an important role in preventing pneumococcal co-infections and combating AMR in all populations, and should be considered a key component of influenza pandemic preparedness or early action plans.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Streptococcus pneumoniae; antimicrobial resistance; pandemic influenza; secondary pneumococcal pneumonia

PMID: 31096052 DOI: 10.1016/j.ijid.2019.05.005

Keywords: Pandemic Influenza; Streptococcus pneumoniae; Vaccines; Antibiotics; Drugs Resistance.


Immunogenicity of full and #fractional dose of inactivated #poliovirus #vaccine for use in routine immunisation and #outbreak response: an open-label, #RCT (Lancet, abstract)

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

Immunogenicity of full and fractional dose of inactivated poliovirus vaccine for use in routine immunisation and outbreak response: an open-label, randomised controlled trial

Cynthia J Snider, PhD, Khalequ Zaman, PhD, Concepcion F Estivariz, MD, Mohammad Yunus, MScCHDC, William C Weldon, PhD, Kathleen A Wannemuehler, PhD, M Steven Oberste, PhD, Mark A Pallansch, PhD, Steven GF Wassilak, MD, Tajul Islam A Bari, MPHM †, Abhijeet Anand, MBBS

Published: May 16, 2019 / DOI:




Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response.


We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered, number NCT02847026.


Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73–83]) versus 305 (57% [53–61]) participants, the type 2 response comprised 173 (64% [58–70]) versus 249 (46% [42–51]) participants, and the type 3 response comprised 196 (73% [67–78]) versus 196 (36% [33–41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vsgroup A) for serotype 1 (−1·12% [90% CI −2·18 to −0·06]), serotype 2 (0·40%, [–2·22 to 1·42]), and serotype 3 (1·51% [–3·23 to −0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV.


fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses.


US Centers for Disease Control and Prevention.

Keywords: Poliovirus; Vaccines.