scholarly journals Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sigrid Gouma ◽  
Kangchon Kim ◽  
Madison E. Weirick ◽  
Megan E. Gumina ◽  
Angela Branche ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
H3n2 Virus ◽  
Virus Infections ◽  
Middle Aged ◽  
Viral Susceptibility ◽  
Cell Responses ◽  
1960S And 1970S ◽  
H3n2 Influenza ◽  
The 1960S

Abstract Influenza virus exposures in childhood can establish long-lived memory B cell responses that can be recalled later in life. Here, we complete a large serological survey to elucidate the specificity of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We find that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. We find that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility.

scholarly journals Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility

2020 ◽  
Author(s):  
Sigrid Gouma ◽  
Kangchon Kim ◽  
Madison Weirick ◽  
Megan E. Gumina ◽  
Angela Branche ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Virus Infections ◽  
Middle Aged ◽  
Viral Susceptibility ◽  
Antibody Titers ◽  
1960S And 1970S ◽  
H3n2 Influenza ◽  
The 1960S

Most humans are infected with influenza viruses by 3-4 years of age (1) and have high antibody titers against viral strains encountered early in life (2). Early childhood influenza exposures can leave lifelong ‘immunological imprints’ that affect how an individual responds to antigenically distinct viral strains later in life (3,4). H3N2 influenza viruses began circulating in humans in 1968 and have evolved substantially over the past 51 years (5). Therefore, an individual’s birth year largely predicts which specific type of H3N2 virus they first encountered in childhood. Here, we completed a large serological survey to elucidate the specificity of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We found that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. Most importantly, we found that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility.

scholarly journals Elicitation of Protective Antibodies against 20 Years of Future H3N2 Cocirculating Influenza Virus Variants in Ferrets Preimmune to Historical H3N2 Influenza Viruses

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
James D. Allen ◽  
Hyesun Jang ◽  
Joshua DiNapoli ◽  
Harold Kleanthous ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
Influenza Viruses ◽  
Human Condition ◽  
World Health ◽  
Virus Infections ◽  
Wild Type ◽  
Virus Like Particle ◽  
Protective Antibodies ◽  
H3n2 Influenza

ABSTRACTThe vast majority of people already have preexisting immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically naive animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 COBRA HA-based vaccines boosted preexisting antibodies induced by wild-type H1N1 virus infections. These H1 COBRA hemagglutinin (HA) antigens induced antibodies with HAI activity against multiple antigenically different H1N1 viral variants. In this study, ferrets, preimmune to historical H3N2 viruses, were vaccinated with virus-like particle (VLP) vaccines expressing either an HA from a wild-type H3 influenza virus or a COBRA H3 HA antigen (T6, T7, T10, or T11). The elicited antisera had the ability to neutralize virus infection against either a panel of viruses representing vaccine strains selected by the World Health Organization or a set of viral variants that cocirculated during the same time period. Preimmune animals vaccinated with H3 COBRA T10 HA antigen elicited sera with higher hemagglutination inhibition (HAI) antibody titers than antisera elicited by VLP vaccines with wild-type HA VLPs in preimmune ferrets. However, while the T11 COBRA vaccine did not elicit HAI activity, the elicited antibodies did neutralize antigenically distinct H3N2 influenza viruses. Overall, H3 COBRA-based HA vaccines were able to neutralize both historical H3 and contemporary, as well as future, H3N2 viruses with higher titers than vaccines with wild-type H3 HA antigens. This is the first report demonstrating the effectiveness of a broadly reactive H3N3 vaccine in a preimmune ferret model.IMPORTANCEAfter exposure to influenza virus, the host generates neutralizing anti-hemagglutinin (anti-HA) antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, cocirculating strains. The goal of next-generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular those that persist over multiple influenza seasons, without requiring an update to the vaccine. To mimic the human condition, COBRA HA virus-like particle vaccines were tested in ferrets that were previously exposed to historical H3N2 influenza viruses. In this model, these vaccines elicited broadly protective antibodies that neutralized cocirculating H3N2 influenza viruses isolated over a 20-year period. This is the first study to show the effectiveness of H3N3 COBRA HA vaccines in a host with preexisting immunity to influenza.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

scholarly journals Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
B F Koel ◽  
R M Vigeveno ◽  
M Pater ◽  
S M Koekkoek ◽  
A X Han ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
De Novo ◽  
Diagnostic Testing ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
H3n2 Virus ◽  
Virus Population ◽  
Sample Collection ◽  
Routine Surveillance ◽  
H3n2 Influenza

Abstract Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4–7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.

scholarly journals A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

2021 ◽  
Author(s):  
Jenna J. Guthmiller ◽  
Julianna Han ◽  
Henry A. Utset ◽  
Lei Li ◽  
Linda Yu-Ling Lan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Human Memory ◽  
Influenza Virus Vaccine ◽  
Virus Infections ◽  
Broadly Neutralizing Antibodies ◽  
Cell Repertoire ◽  
Influenza Virus Hemagglutinin

SummaryBroadly neutralizing antibodies against influenza virus hemagglutinin (HA) have the potential to provide universal protection against influenza virus infections. Here, we report a distinct class of broadly neutralizing antibodies targeting an epitope toward the bottom of the HA stalk domain where HA is “anchored” to the viral membrane. Antibodies targeting this membrane-proximal anchor epitope utilized a highly restricted repertoire, which encode for two conserved motifs responsible for HA binding. Anchor targeting B cells were common in the human memory B cell repertoire across subjects, indicating pre-existing immunity against this epitope. Antibodies against the anchor epitope at both the serological and monoclonal antibody levels were potently induced in humans by a chimeric HA vaccine, a potential universal influenza virus vaccine. Altogether, this study reveals an underappreciated class of broadly neutralizing antibodies against H1-expressing viruses that can be robustly recalled by a candidate universal influenza virus vaccine.

The Sexual Clock: Middle-Aged American Women and Sexual Vitality in the 1960s and 1970s

2020 ◽  
Vol 53 (4) ◽  
pp. 922-938
Author(s):  
Leslie Paris
Keyword(s):  
Intimate Relationships ◽  
Middle Age ◽  
Sexual Revolution ◽  
Sexual Pleasure ◽  
Middle Aged ◽  
Significant Challenge ◽  
Body Project ◽  
Self Actualization ◽  
1960S And 1970S ◽  
The 1960S

Abstract In the wake of the “sexual revolution” of the 1960s and 1970s, a new American consensus emerged both that women’s sexual lives remained important past their youth and that women’s sexual pleasure generally increased into middle age. Challenging the idea that older people were (or ought to be) asexual, mainstream pundits suggested ways to retain or even improve one’s sexual vitality into middle age and beyond, and argued that sex itself was both physically and emotionally rejuvenating. New attitudes toward middle-aged women’s sexuality did not entirely supplant a more traditional body project whose focus was physical maintenance, the appearance of youthfulness, and a nostalgic return to the “true” (that is, younger) self. Yet by the 1970s, increasing numbers of middle-aged women began to consider sexual renewal as an avenue for personal and relational growth, sparked by unexpected shifts in midlife, the mainstreaming of feminist critiques of ageism, and a new ethos of self-actualization. The redefinition of sexuality as a lifelong journey enabled middle-aged women to reconsider their intimate relationships and their bodies, rethink their assumptions about age and sexual desirability, and examine their current levels of sexual satisfaction. By defying the notion that aging was inherently shameful and desexualizing for women, sexologists and feminists of the late 1960s and 1970s offered a significant challenge to the “sexual clock” and helped to redefine middle age as a time of continued growth.

scholarly journals Consequences of Immunodominant Epitope Deletion for Minor Influenza Virus-Specific CD8+-T-Cell Responses

2005 ◽  
Vol 79 (7) ◽  
pp. 4329-4339 ◽  
Author(s):  
Samita S. Andreansky ◽  
John Stambas ◽  
Paul G. Thomas ◽  
Weidong Xie ◽  
Richard J. Webby ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza A ◽  
Reverse Genetics ◽  
H3n2 Virus ◽  
Influenza A Viruses ◽  
Cell Responses ◽  
Infected Cells ◽  
H3n2 Influenza

ABSTRACT The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent DbNP366 and DbPA224 epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ KbPB1703 +, CD8+ KbNS2114 +, and CD8+ DbPB1-F262 + T cells were found in the spleen and in the inflammatory population recovered by bronchoalveolar lavage from mice that were first given the −NP−PA H1N1 virus intraperitoneally and then challenged intranasally with the homologous H3N2 virus. The effect was less consistent when this prime-boost protocol was reversed. Also, though the quality of the response measured by cytokine staining showed some evidence of modification when these minor CD8+-T-cell populations were forced to play a more prominent part, the effects were relatively small and no consistent pattern emerged. The magnitude of the enhanced clonal expansion following secondary challenge suggested that the prime-boost with the −NP−PA viruses gave a response overall that was little different in magnitude from that following comparable exposure to the unmanipulated viruses. This was indeed shown to be the case when the total response was measured by ELISPOT analysis with virus-infected cells as stimulators. More surprisingly, the same effect was seen following primary challenge, though individual analysis of the CD8+ KbPB1703 +, CD8+ KbNS2114 +, and CD8+ DbPB1-F262 + sets gave no indication of compensatory expansion. A possible explanation is that novel, as yet undetected epitopes emerge following primary exposure to the −NP−PA deletion viruses. These findings have implications for both natural infections and vaccines.

scholarly journals A liposome-displayed hemagglutinin vaccine platform protects mice and ferrets from heterologous influenza virus challenge

2021 ◽  
Vol 118 (22) ◽  
pp. e2025759118
Author(s):  
Zachary R. Sia ◽  
Xuedan He ◽  
Ali Zhang ◽  
Jann C. Ang ◽  
Shuai Shao ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibodies ◽  
H3n2 Virus ◽  
Antigen Delivery ◽  
Vaccine Platform ◽  
Virus Challenge ◽  
H5n1 Influenza ◽  
Adjuvant System ◽  
Protein Particle

Recombinant influenza virus vaccines based on hemagglutinin (HA) hold the potential to accelerate production timelines and improve efficacy relative to traditional egg-based platforms. Here, we assess a vaccine adjuvant system comprised of immunogenic liposomes that spontaneously convert soluble antigens into a particle format, displayed on the bilayer surface. When trimeric H3 HA was presented on liposomes, antigen delivery to macrophages was improved in vitro, and strong functional antibody responses were induced following intramuscular immunization of mice. Protection was conferred against challenge with a heterologous strain of H3N2 virus, and naive mice were also protected following passive serum transfer. When admixed with the particle-forming liposomes, immunization reduced viral infection severity at vaccine doses as low as 2 ng HA, highlighting dose-sparing potential. In ferrets, immunization induced neutralizing antibodies that reduced the upper respiratory viral load upon challenge with a more modern, heterologous H3N2 viral strain. To demonstrate the flexibility and modular nature of the liposome system, 10 recombinant surface antigens representing distinct influenza virus strains were bound simultaneously to generate a highly multivalent protein particle that with 5 ng individual antigen dosing induced antibodies in mice that specifically recognized the constituent immunogens and conferred protection against heterologous H5N1 influenza virus challenge. Taken together, these results show that stable presentation of recombinant HA on immunogenic liposome surfaces in an arrayed fashion enhances functional immune responses and warrants further attention for the development of broadly protective influenza virus vaccines.

scholarly journals Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8+ T-Cell Responses

2009 ◽  
Vol 84 (4) ◽  
pp. 1847-1855 ◽  
Author(s):  
Scott N. Mueller ◽  
William A. Langley ◽  
Elena Carnero ◽  
Adolfo García-Sastre ◽  
Rafi Ahmed
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
B Cell ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Influenza Viruses ◽  
Wild Type Virus ◽  
Virus Infections ◽  
Cell Responses ◽  
B Cell Responses

ABSTRACT The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8+ T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8+ T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.

Eating amid Affluence

2018 ◽  
Author(s):  
Bruce Suttmeier
Keyword(s):  
Complex Relationship ◽  
The Novel ◽  
Middle Aged ◽  
1960S And 1970S ◽  
The 1960S ◽  
Budget Surplus

This chapter investigates the tensions between the pleasures and discomforts of indulgence in the 1960s and 1970s, an era of growing affluence and consumption, through the work of writer Kaikō Takeshi (1930–1989), who frequently waxed rhapsodically and nostalgically about his favorite foods in essays and novels. In his satiric 1972 serial A New Star, a middle-aged bureaucrat is ordered to literally eat his ministry’s budget surplus through lavish meals and regional excursions to consume local delicacies. The chapter observes that, while the novel can be read as a critique of consumption and government waste, there is also a nostalgic tone to Kaikō’s final inventory of dishes that suggests both the pleasure and pain of overconsumption and thus reflects the complex relationship between duty and desire.

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