Influenza A neuraminidase antibodies in children and young adults studied by serum absorption

SUMMARYA study is described of influenza A anti-neuraminidase antibodies in the sera of young people of three different age groups. Each serum was individually absorbed with viruses containing the N2 neuraminidases of 1957, 1968 and 1972. Rabbit antisera prepared against the viruses were similarly absorbed. Results obtained with the animal sera suggested that these neuraminidases were antigenically distinct, but the human sera had a broader range of anti-neuraminidase activity and gave indication of asymmetric antigenic relationships. Earlier workers who surveyed anti-haemagglutinin antibodies reported that the virus of primary infection absorbed all antibodies, and the virus of secondary infection only those directed against itself. We too found that the virus of secondary infection absorbed only homologous anti-neuraminidase antibody. However, although the primary infecting virus did absorb some secondary antibody, this absorption was incomplete and it lessened with the lengthening of the time interval between the primary and secondary infecting viruses. A similar pattern was seen with anti-haemagglutinin antibodies.Absorption of anti-neuraminidase antibodies from human sera proved much more difficult than absorption of anti-haemagglutinin antibodies particularly after repeated influenza virus infections. The relative rarity of antigenic shift in the neuraminidase subunit also creates problems in the interpretation of results of serum neuraminidase antibody surveys.

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Clinical and epidemiological characteristics of acute respiratory virus infections in Vietnamese children

Epidemiology and Infection ◽

10.1017/s095026881500134x ◽

2015 ◽

Vol 144 (3) ◽

pp. 527-536 ◽

Cited By ~ 10

Author(s):

D. N. TRAN ◽

Q. D. TRINH ◽

N. T. K. PHAM ◽

M. P. VU ◽

M. T. HA ◽

...

Keyword(s):

Influenza A ◽

Respiratory Infections ◽

Age Groups ◽

Ho Chi Minh City ◽

Human Bocavirus ◽

Virus Infections ◽

Polymerase Chain ◽

Syncytial Virus ◽

Respiratory Virus Infections ◽

Epidemiological Characteristics

SUMMARYInformation about viral acute respiratory infections (ARIs) is essential for prevention, diagnosis and treatment, but it is limited in tropical developing countries. This study described the clinical and epidemiological characteristics of ARIs in children hospitalized in Vietnam. Nasopharyngeal samples were collected from children with ARIs at Ho Chi Minh City Children's Hospital 2 between April 2010 and May 2011 in order to detect respiratory viruses by polymerase chain reaction. Viruses were found in 64% of 1082 patients, with 12% being co-infections. The leading detected viruses were human rhinovirus (HRV; 30%), respiratory syncytial virus (RSV; 23·8%), and human bocavirus (HBoV; 7·2%). HRV was detected all year round, while RSV epidemics occurred mainly in the rainy season. Influenza A (FluA) was found in both seasons. The other viruses were predominant in the dry season. HRV was identified in children of all age groups. RSV, parainfluenza virus (PIV) 1, PIV3 and HBoV, and FluA were detected predominantly in children aged <6 months, 6–12 months, 12–24 months, and >24 months, respectively. Significant associations were found between PIV1 with croup (P < 0·005) and RSV with bronchiolitis (P < 0·005). HBoV and HRV were associated with hypoxia (P < 0·05) and RSV with retraction (P < 0·05). HRV, RSV, and HBoV were detected most frequently and they may increase the severity of ARIs in children.

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Age-specific differences in the dynamics of protective immunity to influenza

10.1101/330720 ◽

2018 ◽

Cited By ~ 2

Author(s):

Sylvia Ranjeva ◽

Rahul Subramanian ◽

Vicky J. Fang ◽

Gabriel M. Leung ◽

Dennis K. M. Ip ◽

...

Keyword(s):

Protective Immunity ◽

Influenza A ◽

Influenza Infection ◽

Age Groups ◽

Virus Infections ◽

Influenza A Viruses ◽

Individual Level ◽

Antibody Titers ◽

Original Antigenic Sin ◽

Changes Over Time

AbstractInfluenza A viruses evolve rapidly to escape host immunity, such that individuals can be infected multiple times with the same subtype. The form and duration of protective immunity after each influenza infection are poorly understood. Here, we quantify the dynamics of protective immunity against influenza A virus infections by fitting individual-level mechanistic models to longitudinal serology from children and adults in a household cohort study. We find that most protection in children is explained by antibody titers measured by the hemagglutination inhibition (HI) assay. In contrast, in adults, HI antibody titers explain a smaller fraction of protection. Protection against circulating strains wanes to approximately 50% of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that the focus of influenza antibody responses changes over time from the highly mutable hemagglutinin head to other epitopes, consistent with the immunological theory of original antigenic sin, and that this change of focus might affect protection. Additionally, we estimate that imprinting, or primary infection with a subtype of one phylogenetic group, has little to no effect on the risk of non-medically attended influenza infections in adults. We also find no evidence of long-term cross-protection between subtypes. This work underscores the need for longitudinal data on multiple components of the immune response to better understand the development of immunity and differences in susceptibility within populations.

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Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa161 ◽

2020 ◽

Vol 222 (1) ◽

pp. 9-16 ◽

Cited By ~ 38

Author(s):

Arnold S Monto ◽

Peter M DeJonge ◽

Amy P Callear ◽

Latifa A Bazzi ◽

Skylar B Capriola ◽

...

Keyword(s):

Influenza A ◽

Respiratory Infections ◽

Secondary Infection ◽

Age Groups ◽

Infection Risk ◽

Infection Frequency ◽

Transmission Potential ◽

Time Period ◽

Serial Interval ◽

Human Coronaviruses

Abstract Background As part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults from 2010 to 2018. Methods Annually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63. Results In total, 993 HCoV infections were identified during the 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range, 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type. Conclusions Coronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.

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A Simple Mathematical Model Helps To Explain the Immunodominance of CD8 T Cells in Influenza A Virus Infections

Journal of Virology ◽

10.1128/jvi.00653-08 ◽

2008 ◽

Vol 82 (16) ◽

pp. 7768-7772 ◽

Cited By ~ 21

Author(s):

Andreas Handel ◽

Rustom Antia

Keyword(s):

Mathematical Model ◽

T Cells ◽

Influenza A Virus ◽

Influenza A ◽

Secondary Infection ◽

Initial Response ◽

Secondary Response ◽

Simple Mathematical Model ◽

Virus Infections ◽

Dynamic Interactions

ABSTRACT Understanding immunodominance, the phenomenon of epitope-specific T cells expanding in an often distinctly hierarchical fashion, is important for the design of T-cell-based intervention strategies. Several recent studies have investigated immunodominance of H-2Db-restricted CD8+ T cells specific for the nucleoprotein NP366 and acid polymerase PA224 epitopes during influenza A virus infection of C57BL/6 mice. CD8+ T cells specific for these two epitopes are codominant during primary infection; NP366 dominates during secondary infection. While a number of explanations for this observation have been proposed, none of them can fully account for all the observed data. In this article, we use a simple mathematical model to explain the seemingly inconsistent data. We show that the dynamic interactions between CD8+ T cells and antigen presentation lead to a situation where CD8+ T cells are limiting during the initial response whereas antigen is limiting in the secondary response. This “numbers game” between antigen and CD8+ T cells can reproduce the observed immunodominance of the NP336- and PA224-specific CD8+ T cells, thereby explaining the reported experimental data.

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

Scientific Reports ◽

10.1038/s41598-020-79590-7 ◽

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.

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Letter to the Editor: Microbiota in the Respiratory System—A Possible Explanation to Age and Sex Variability in Susceptibility to SARS-CoV-2

Microbiology Insights ◽

10.1177/1178636120988604 ◽

2021 ◽

Vol 14 ◽

pp. 117863612098860

Author(s):

Vishal Shah

Keyword(s):

Respiratory System ◽

Elderly Population ◽

Age Groups ◽

The Elderly ◽

Elderly Adult ◽

Human Respiratory Tract ◽

System A ◽

Number Of Patients ◽

Children And Young Adults ◽

Age And Sex

The Human respiratory tract is colonized by a variety of microbes and the microbiota change as we age. In this perspective, literature support is presented for the hypothesis that the respiratory system microbiota could explain the differential age and sex breakdown amongst COVID-19 patients. The number of patients in the older and elderly adult group is higher than the other age groups. The perspective presents the possibility that certain genera of bacteria present in the respiratory system microbiota in children and young adults could be directly or through eliciting an immune response from the host, prevent full-fledged infection of SARS-CoV-2. The possibility also exists that the microbiota in older adults and the elderly population have bacteria that make it easier for the virus to cause infection. I call upon the scientific community to investigate the link between human microbiota and SARS-CoV-2 susceptibility to further understand the viral pathogenesis.

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Epidemiology of West Nile Virus Infections in Humans, Italy, 2012–2020: A Summary of Available Evidences

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6020061 ◽

2021 ◽

Vol 6 (2) ◽

pp. 61

Author(s):

Matteo Riccò ◽

Simona Peruzzi ◽

Federica Balzarini

Keyword(s):

West Nile Virus ◽

Age Groups ◽

Invasive Disease ◽

Incidence Rates ◽

Annual Incidence ◽

Virus Infections ◽

West Nile ◽

Po River ◽

Air Temperatures ◽

Sex Risk

In Italy, human cases of West Nile virus (WNV) infection have been recorded since 2008, and seasonal outbreaks have occurred almost annually. In this study, we summarize available evidences on the epidemiology of WNV and West Nile neuro-invasive disease (WNND) in humans reported between 2012 and 2020. In total, 1145 WNV infection cases were diagnosed; of them 487 (42.5%) had WNND. A significant circulation of the pathogen was suggested by studies on blood donors, with annual incidence rates ranging from 1.353 (95% confidence intervals (95% CI) 0.279–3.953) to 19.069 cases per 100,000 specimens (95% CI 13.494–26.174). The annual incidence rates of WNND increased during the study period from 0.047 cases per 100,000 (95% CI 0.031–0.068) in 2012, to 0.074 cases per 100,000 (95% CI 0.054–0.099) in 2020, peaking to 0.377 cases per 100,000 (95% CI 0.330–0.429) in 2018. There were 60 deaths. Cases of WNND were clustered in Northern Italy, particularly in the Po River Valley, during the months of August (56.7%) and September (27.5%). Higher risk for WNND was reported in subjects of male sex (risk ratio (RR) 1.545, 95% CI 1.392–1.673 compared to females), and in older age groups (RR 24.46, 95% CI 15.61–38.32 for 65–74 y.o.; RR 43.7, 95% CI 28.33–67.41 for subjects older than 75 years), while main effectors were identified in average air temperatures (incidence rate ratio (IRR) 1.3219, 95% CI 1.0053–1.7383), population density (IRR 1.0004, 95% CI 1.0001–1.0008), and occurrence of cases in the nearby provinces (IRR 1.0442, 95% CI 1.0340–1.0545). In summary, an enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

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Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review

Oxford Open Immunology ◽

10.1093/oxfimm/iqab001 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Felix Clemens Richter ◽

Aljawharah Alrubayyi ◽

Alicia Teijeira Crespo ◽

Sarah Hulin-Curtis ◽

Keyword(s):

Lipid Metabolism ◽

Influenza A ◽

Immune Cell ◽

Cell Metabolism ◽

Low Grade ◽

Obese Patients ◽

Healthy Weight ◽

Virus Infections ◽

Immune Alterations ◽

And Function

Abstract The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host’s altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

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Exacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01664-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6328-6333 ◽

Cited By ~ 15

Author(s):

Donald F. Smee ◽

Mark von Itzstein ◽

Beenu Bhatt ◽

E. Bart Tarbet

Keyword(s):

Influenza Virus ◽

Influenza A ◽

H1n1 Virus ◽

Antiviral Agent ◽

Virus Production ◽

Lung Pathology ◽

Virus Infections ◽

Challenge Dose ◽

Virus Challenge ◽

Time To Death

ABSTRACTCompounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.

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