scholarly journals The impact of seasonal and year-round transmission regimes on the evolution of influenza A virus

2010 ◽  
Vol 278 (1716) ◽  
pp. 2249-2256 ◽  
Author(s):  
Ben Adams ◽  
Alice Carolyn McHardy
Keyword(s):  
Influenza A ◽  
Evolutionary Dynamics ◽  
Vaccine Development ◽  
Herd Immunity ◽  
Wild Type ◽  
Critical Window ◽  
Seasonal Transmission ◽  
Seasonal Epidemics ◽  
Seasonal Circulation ◽  
The Impact

Punctuated antigenic change is believed to be a key element in the evolution of influenza A; clusters of antigenically similar strains predominate worldwide for several years until an antigenically distant mutant emerges and instigates a selective sweep. It is thought that a region of East–Southeast Asia with year-round transmission acts as a source of antigenic diversity for influenza A and seasonal epidemics in temperate regions make little contribution to antigenic evolution. We use a mathematical model to examine how different transmission regimes affect the evolutionary dynamics of influenza over the lifespan of an antigenic cluster. Our model indicates that, in non-seasonal regions, mutants that cause significant outbreaks appear before the peak of the wild-type epidemic. A relatively large proportion of these mutants spread globally. In seasonal regions, mutants that cause significant local outbreaks appear each year before the seasonal peak of the wild-type epidemic, but only a small proportion spread globally. The potential for global spread is strongly influenced by the intensity of non-seasonal circulation and coupling between non-seasonal and seasonal regions. Results are similar if mutations are neutral, or confer a weak to moderate antigenic advantage. However, there is a threshold antigenic advantage, depending on the non-seasonal transmission intensity, beyond which mutants can escape herd immunity in the non-seasonal region and there is a global explosion in diversity. We conclude that non-seasonal transmission regions are fundamental to the generation and maintenance of influenza diversity owing to their epidemiology. More extensive sampling of viral diversity in such regions could facilitate earlier identification of antigenically novel strains and extend the critical window for vaccine development.

scholarly journals Characterization of the evolutionary dynamics of influenza A H3N2 hemagglutinin

2020 ◽  
Author(s):  
Maggie Haitian Wang ◽  
Jingzhi Lou ◽  
Lirong Cao ◽  
Shi Zhao ◽  
Paul KS Chan ◽  
...  
Keyword(s):  
North America ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Herd Immunity ◽  
Genomic Region ◽  
Point Of View ◽  
Population Immunity ◽  
Epidemiology Data ◽  
Mutation Dynamics

AbstractVirus evolution drives the annual influenza epidemics in human population worldwide. However, it has been challenging to evaluate the mutation effect of the influenza virus on evading the population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics by the effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by the effective mutation periods (EMPs). Extensive analysis is performed on the genome and epidemiology data of 13-year worldwide H3N2 epidemics involving nine regions in four continents. We showed that the identified EM processed similar profile in geographically adjacent regions, while only 40% are common to Europe, North America, Asia and Oceania, indicating that the regional specific mutations also contributed significantly to the global H3N2 epidemics. The mutation dynamics calibrated that around 90% of the common EMs underlying global epidemics were originated from South East Asia, led by Thailand and India, and the rest were originated from North America. New Zealand was found to be the dominate sink region of H3N2 circulation, followed by UK. All regions might act as the intersection in the H3N2 transmission network. The proposed methodology provided a way to characterize key amino acids from the genetic epidemiology point of view. This approach is not restricted by the genomic region or type of the virus, and will find broad applications in identifying therapeutic targets for combating infectious diseases.

The impact of antigenic drift of influenza A virus on human herd immunity: Sero-epidemiological study of H1N1 in healthy Thai population in 2009

Vaccine ◽  
2010 ◽  
Vol 28 (33) ◽  
pp. 5437-5444 ◽  
Author(s):  
Yuta Kanai ◽  
Naphatsawan Boonsathorn ◽  
Malinee Chittaganpitch ◽  
Guirong Bai ◽  
Yonggang Li ◽  
...  
Keyword(s):  
Epidemiological Study ◽  
Influenza A Virus ◽  
Influenza A ◽  
Herd Immunity ◽  
Antigenic Drift ◽  
Thai Population ◽  
The Impact

scholarly journals Influenza A virus hemagglutinin mutations associated with use of neuraminidase inhibitors correlate with decreased inhibition by anti-influenza antibodies

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Natalia A. Ilyushina ◽  
Takashi E. Komatsu ◽  
William L. Ince ◽  
Eric F. Donaldson ◽  
Nicolette Lee ◽  
...  
Keyword(s):  
Influenza A ◽  
Wild Type Virus ◽  
Epithelial Cell Line ◽  
Immune Reactivity ◽  
Neuraminidase Inhibitors ◽  
Type Virus ◽  
Wild Type ◽  
Serum Samples ◽  
Influenza Hemagglutinin ◽  
The Impact

Abstract Background Vaccination and the use of neuraminidase inhibitors (NAIs) are currently the front lines of defense against seasonal influenza. The activity of influenza vaccines and antivirals drugs such as the NAIs can be affected by mutations in the influenza hemagglutinin (HA) protein. Numerous HA substitutions have been identified in nonclinical NAI resistance-selection experiments as well as in clinical specimens from NAI treatment or surveillance studies. These mutations are listed in the prescribing information (package inserts) for FDA-approved NAIs, including oseltamivir, zanamivir, and peramivir. Methods NAI treatment-emergent H1 HA mutations were mapped onto the H1N1 HA1 trimeric crystal structure and most of them localized to the HA antigenic sites predicted to be important for anti-influenza immunity. Recombinant A/California/04/09 (H1N1)-like viruses carrying HA V152I, G155E, S162 N, S183P, and D222G mutations were generated. We then evaluated the impact of these mutations on the immune reactivity and replication potential of the recombinant viruses in a human respiratory epithelial cell line, Calu− 3. Results We found that the G155E and D222G mutations significantly increased viral titers ~ 13-fold compared to the wild-type virus. The hemagglutination and microneutralization activity of goat and ferret antisera, monoclonal antibodies, and human serum samples raised against pandemic A(H1N1)pdm09 viruses was ~ 100-fold lower against mutants carrying G155E or D222G compared to the wild-type virus. Conclusions Although the mechanism by which HA mutations emerge during NAI treatment is uncertain, some NAI treatment-emergent HA mutations correlate with decreased immunity to influenza virus.

scholarly journals 2750. Sequential Influenza A H1N1 and Influenza A H3N2 Challenge Infections in Healthy Volunteers

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S969-S969 ◽  
Author(s):  
Alison Han ◽  
Luca Giurgea ◽  
Adriana Cervantes-Medina ◽  
Kristina Edwards ◽  
Luz Angela Rosas ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Influenza A ◽  
Reverse Genetics ◽  
Clinical Symptoms ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Wild Type ◽  
Viral Shedding ◽  
Influenza A H1n1 ◽  
The Impact

Abstract Background Seasonal influenza causes significant annual morbidity and mortality. The effects of yearly exposures on immunity are not clear and recent observations have demonstrated that long lasting protection against a matched strain may not naturally occur. The 2018–2019 influenza season consisted of an initial peak of H1N1 infections followed by a wave of H3N2 infections. These consecutive waves raise questions about how influenza immunity is affected by sequential exposure to different influenza strains. Challenge studies provide a unique opportunity to study this phenomenon. Here we describe a subset of participants who were sequentially infected in two separate challenge studies with wild-type H1N1 and H3N2 viruses. Methods Healthy volunteers completed two sequential influenza challenge studies at the NIH Clinical Center. Participants were inoculated with reverse genetics, cell-based, GMP wild-type influenza viruses, A(H1N1)pdm09 and A(H3N2) strains. Participants remained isolated in the hospital for a minimum of 9 days and were monitored daily for viral shedding and clinical symptoms. After discharge, participants were followed for 2 months. Results Between 2014 and 2017, 14 healthy volunteers were exposed to Influenza A(H1N1) and Influenza A(H3N2). Time between infections ranged from 2 months to 2 years. Thirteen (93%) participants developed confirmed influenza infection after H1N1 challenge and 9 (64%) after H3N2 challenge. Eight (57%) participants developed confirmed infections after both exposures. Variable degrees of symptoms, shedding, and disease severity were observed. Systemic antibody responses to the HA and NA of both H1N1 and H3N2 varied over time during these sequential infections. Conclusion More than half of all participants who completed 2 sequential H1N1 and H3N2 challenge studies demonstrated confirmed infection to both viruses. These sequential infections had varying effects on the disease experienced and the immunity that developed after infection. These observations are important in understanding the impact of sequential exposures on influenza immunity. Disclosures All authors: No reported disclosures.

scholarly journals Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics

2019 ◽  
Author(s):  
Katelyn M Gostic ◽  
Rebecca Bridge ◽  
Shane Brady ◽  
Cécile Viboud ◽  
Michael Worobey ◽  
...  
Keyword(s):  
Influenza A ◽  
Model Comparison ◽  
Seasonal Influenza ◽  
Evolutionary Rate ◽  
Epidemiological Surveillance ◽  
Immune Memory ◽  
Childhood Exposure ◽  
Seasonal Epidemics ◽  
Middle Aged Adults ◽  
The Impact

AbstractAcross decades of co-circulation in humans, influenza A subtypes H1N1 and H3N2 have caused seasonal epidemics characterized by different age distributions of infection and mortality. H3N2 causes the majority of cases in high-risk elderly cohorts, and the majority of overall deaths, whereas H1N1 causes incidence shifted towards young and middle-aged adults, and fewer deaths. These contrasting age profiles may result from differences in childhood exposure to H1N1 and H3N2 or from differences in evolutionary rate between subtypes. Here we analyze a large epidemiological surveillance dataset to test whether childhood immune imprinting shapes seasonal influenza epidemiology, and if so, whether it acts primarily via immune memory of a particular influenza subtype or via broader immune memory that protects across subtypes. We also test the impact of evolutionary differences between influenza subtypes on age distributions of infection. Likelihood-based model comparison shows that narrow, within-subtype imprinting is the strongest driver of seasonal influenza risk. The data do not support a strong effect of evolutionary rate, or of broadly protective imprinting that acts across subtypes. Our findings emphasize that childhood exposures can imprint a lifelong immunological bias toward particular influenza subtypes, and that these cohort-specific biases shape epidemic age distributions. As a result, newer and less “senior” antibody responses acquired later in life do not provide the same strength of protection as responses imprinted in childhood. Finally, we project that the relatively low mortality burden of H1N1 may increase in the coming decades, as cohorts that lack H1N1-specific imprinting eventually reach old age.

scholarly journals Impact of a Black Physician Panel Discussion on Coronavirus Disease 2019 (COVID-19) Health Education

2021 ◽  
Vol 1 (S1) ◽  
pp. s1-s1
Author(s):  
Kenisha Evans ◽  
Jannel Lee-Allen ◽  
Donald Chinemelu Okoye ◽  
Lauren Uroda ◽  
Teena Chopra ◽  
...  
Keyword(s):  
Social Media ◽  
Vaccine Development ◽  
Panel Discussion ◽  
Herd Immunity ◽  
Vaccine Safety ◽  
The United States ◽  
Medical Mistrust ◽  
Media Campaign ◽  
Black Physicians ◽  
The Impact

Background: Coronavirus disease 19 (COVID-19) has infected >26 million Americans with >400,000 deaths. Both Pfizer and Moderna vaccines against severe acute respiratory coronavirus 2 (SARS-CoV-2) have demonstrated 95% efficacy; yet there has been growing vaccination hesitancy, especially within communities of color. To achieve herd immunity and quell the spread of SARS-CoV-2, several strategies need to be deployed. This community-based demonstration project highlights the impact of a panel of black physicians’ ability to increase vaccination intent within a social media campaign targeted toward a black audience, namely a live question-and-answer (Q&A) event on SARS-CoV-2 vaccines. Methods: The social media campaign included a flyer featuring the head shots and titles of 11 black physicians. The flyer showcased a live Q&A event via Zoom video conference software. Attendees were requested to preregister with their name, e-mail address, and country of origin. Results: The live Q&A event was attended by 251 viewers. Geographic distribution was predominantly within the United States (~88%), but a few attendees were from the United Kingdom (~11%) and Canada (<1%), Puerto Rico (<1%), and Paraguay (<1%). One hundred twenty eight questions and comments were received from attendees. Audience questions were categorized, with predominant topics as follows: Vaccine Safety, Medical Mistrust, Vaccine Safety in Pregnancy, Vaccine Efficacy, and Vaccine Development. The top five poll results revealed: 31% of audience members were not planning to vaccinate or were not sure about vaccination, but after the event are now planning to vaccinate; 93% believed their knowledge of the C19 vaccines had increased; 95% believed it was important that the information was presented by Black health experts; 90% reported that they trusted the information presented; and 96% rated the session as “good or excellent”. Conclusion: Our social media project is an example of one strategy healthcare professionals can utilize to positively influence local and global communities in the mitigation of the COVID-19 pandemic. Results of this project evaluation showed that viewers responded favorably, reporting increases in vaccine acceptance and knowledge. Most respondents also affirmed the importance of having black experts involved in communicating this information. COVID-19 has disproportionately affected black communities as a result of health inequities and institutionalized racism.1 The event amplifies the importance of utilizing social-media–based interventions and increasing black healthcare representation to aid infection control. 1. Jones C. Why Racism, Not Race, Is a Risk Factor for Dying of COVID-19. Scientific American June 12, 2020.Funding: NoDisclosures: None

Subtle Impact of Akt1 and Akt3 on Exploratory Behavior in Gene Targeted Mice

2015 ◽  
Vol 223 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Christina Leibrock ◽  
Michael Hierlmeier ◽  
Undine E. Lang ◽  
Florian Lang
Keyword(s):  
Forced Swimming Test ◽  
Open Field Test ◽  
Wild Type ◽  
Average Speed ◽  
Closed Area ◽  
Light Area ◽  
Swimming Test ◽  
The Impact ◽  
Center Area ◽  
Dark Transition

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.

SARS-CoV-2 Biology Insights, Part IV.Antibody-Dependent Enhancement (ADE) and the tricky “Herd Immunity”: narrative review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Whooping Cough ◽  
Common Knowledge ◽  
Herd Immunity ◽  
Life Quality ◽  
Host Cells ◽  
System P

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

scholarly journals Estimating asymptomatic, undetected and total cases for the COVID-19 outbreak in Wuhan: a mathematical modeling study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xi Huo ◽  
Jing Chen ◽  
Shigui Ruan
Keyword(s):  
Disease Transmission ◽  
Large Scale ◽  
Transmission Rate ◽  
Control Strategies ◽  
Herd Immunity ◽  
Antibody Prevalence ◽  
Screening Process ◽  
Vaccination Programs ◽  
Prevalence Level ◽  
The Impact

Abstract Background The COVID-19 outbreak in Wuhan started in December 2019 and was under control by the end of March 2020 with a total of 50,006 confirmed cases by the implementation of a series of nonpharmaceutical interventions (NPIs) including unprecedented lockdown of the city. This study analyzes the complete outbreak data from Wuhan, assesses the impact of these public health interventions, and estimates the asymptomatic, undetected and total cases for the COVID-19 outbreak in Wuhan. Methods By taking different stages of the outbreak into account, we developed a time-dependent compartmental model to describe the dynamics of disease transmission and case detection and reporting. Model coefficients were parameterized by using the reported cases and following key events and escalated control strategies. Then the model was used to calibrate the complete outbreak data by using the Monte Carlo Markov Chain (MCMC) method. Finally we used the model to estimate asymptomatic and undetected cases and approximate the overall antibody prevalence level. Results We found that the transmission rate between Jan 24 and Feb 1, 2020, was twice as large as that before the lockdown on Jan 23 and 67.6% (95% CI [0.584,0.759]) of detectable infections occurred during this period. Based on the reported estimates that around 20% of infections were asymptomatic and their transmission ability was about 70% of symptomatic ones, we estimated that there were about 14,448 asymptomatic and undetected cases (95% CI [12,364,23,254]), which yields an estimate of a total of 64,454 infected cases (95% CI [62,370,73,260]), and the overall antibody prevalence level in the population of Wuhan was 0.745% (95% CI [0.693%,0.814%]) by March 31, 2020. Conclusions We conclude that the control of the COVID-19 outbreak in Wuhan was achieved via the enforcement of a combination of multiple NPIs: the lockdown on Jan 23, the stay-at-home order on Feb 2, the massive isolation of all symptomatic individuals via newly constructed special shelter hospitals on Feb 6, and the large scale screening process on Feb 18. Our results indicate that the population in Wuhan is far away from establishing herd immunity and provide insights for other affected countries and regions in designing control strategies and planing vaccination programs.

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