The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals

ABSTRACTThe microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.

Download Full-text

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Journal of Virology ◽

10.1128/jvi.01323-18 ◽

2018 ◽

Vol 92 (22) ◽

Cited By ~ 5

Author(s):

Eugenio J. Abente ◽

Daniela S. Rajao ◽

Jefferson Santos ◽

Bryan S. Kaplan ◽

Tracy L. Nicholson ◽

...

Keyword(s):

Influenza A Virus ◽

Vaccine Efficacy ◽

Influenza A ◽

Rapid Evolution ◽

The United States ◽

Upper Respiratory Tract ◽

Influenza A Viruses ◽

Partial Protection ◽

Attenuated Virus ◽

The Impact

ABSTRACTInfluenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266–8280, 2016,https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses.IMPORTANCEDue to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.

Download Full-text

Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine

Journal of General Virology ◽

10.1099/vir.0.045005-0 ◽

2012 ◽

Vol 93 (10) ◽

pp. 2204-2214 ◽

Cited By ~ 20

Author(s):

Lindomar Pena ◽

Amy L. Vincent ◽

Crystal L. Loving ◽

Jamie N. Henningson ◽

Kelly M. Lager ◽

...

Keyword(s):

Virus Replication ◽

Influenza A ◽

Reverse Genetics ◽

Influenza Viruses ◽

Dependent Manner ◽

Lung Pathology ◽

Influenza A Viruses ◽

Virus Shedding ◽

The Impact ◽

Strain Dependent

The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.

Download Full-text

Characterization of the utility of three nebulizers in investigating infectivity of airborne viruses

10.1101/2021.03.11.435057 ◽

2021 ◽

Author(s):

Sadegh Niazi ◽

Lisa K. Philp ◽

Kirsten Spann ◽

Graham R. Johnson

Keyword(s):

Infectious Disease ◽

Size Distribution ◽

Normal Saline ◽

Influenza A ◽

Indoor Environments ◽

Influenza A Viruses ◽

Physician Visits ◽

Aerosol Mass ◽

Tract Infections ◽

The Impact

AbstractLaboratory-generated bioaerosols are widely used in aerobiology studies of viruses, however few comparisons of alternative nebulizers exist. We compared aerosol production and virus survival for a Collison nebulizer, vibrating mesh nebulizer (VMN), and hydraulic spray atomizer (HAS). We also measured the dry size distribution of the aerosols produced, calculated the droplet sizes before evaporation and the dry size distribution from normal saline solution. Dry count median diameters of 0.25, 0.63 and 0.76 µm were found for normal saline from the Collison nebulizer, VMN and HSA, respectively. The volume median diameters were 2.91, 3.2 and 2.43 µm, respectively. The effect of nebulization on the viability of two influenza A viruses (IAVs) (H1N1, H3N2) and human rhinovirus (HRV)-16, was assessed by direct nebulization into an SKC Biosampler. The HSA had least impact on surviving fractions (SFs) of H1N1 and H3N2 (89±5%, 94±3%), followed by the Collison nebulizer (82±2%, 82±3%). The VMN yielded SFs of 78±2% and 76±2%, respectively. Conversely, for HRV-16, the VMN produced higher SFs (86±15%). Our findings indicate that although the VMN had the greatest impact on IAV survival, it produced higher aerosol concentrations within the airborne-size range making it more suitable where high aerosol mass production is required.ImportanceViral respiratory tract infections cause millions of lost days of work and physician visits globally, accounting for significant morbidity and mortality. Respiratory droplet and droplet nuclei from infected hosts are the substantial potential carriers of such viruses within indoor environments. Laboratory-generated bioaerosols are applied in understanding the transmission and infection of viruses, simulating the physiological aspects of bioaerosol generation in a controlled environment. However, little comparative characterization exists for nebulizers used in infectious disease aerobiology, including Collison nebulizer, Vibrating mesh nebulizer, and hydraulic spray atomizer. This study characterized the physical features of aerosols generated by laboratory nebulizers, and their performance in producing aerosols at a size relevant to airborne transmission used in infectious disease aerobiology. We also determined the impact of nebulization mechanisms of these nebulizers on the viability of human respiratory viruses, including IAV H1N1, IAV H3N2 and HRV-16.

Download Full-text

High expression levels of influenza virus receptors in airway of the HBV-transgenic mice

Epidemiology and Infection ◽

10.1017/s0950268819001833 ◽

2019 ◽

Vol 147 ◽

Author(s):

Jiajun Yang ◽

Hao Li ◽

Liyuan Jia ◽

Xianchun Lan ◽

Yuhui Zhao ◽

...

Keyword(s):

Influenza Virus ◽

Transgenic Mice ◽

Chronic Diseases ◽

Influenza A ◽

Respiratory Illness ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Expression Levels ◽

Virus Receptors ◽

The Impact

Abstract In the human population, influenza A viruses are associated with acute respiratory illness and are responsible for millions of deaths annually. Avian and human influenza viruses typically have a different α2-3- and α2-6-linked sialic acid (SA) binding preference. Only a few amino acid changes in the haemagglutinin on the surface of avian influenza viruses (AIV) can cause a switch from avian to human receptor specificity, and the individuals with pathognostic chronic diseases might be more susceptible to AIV due to the decreased expression level of terminal α2-3-linked SA in their saliva. Here, using lectin and virus histochemical staining, we observed the higher expression levels of α2-3/6-linked SA influenza virus receptors in the airway of HBV-transgenic mice compared with that of control mice due to the significant decrease in control mice during ageing, which imply that this is also a risk factor for individuals with pathognostic chronic diseases susceptible to influenza viruses. Our findings will help understand the impact on influenza virus pathogenesis and transmission.

Download Full-text

The impact of key amino acid substitutions in the hemagglutinin of influenza A (H3N2) viruses on vaccine production and antibody response

Vaccine ◽

10.1016/j.vaccine.2010.03.078 ◽

2010 ◽

Vol 28 (24) ◽

pp. 4079-4085 ◽

Cited By ~ 50

Author(s):

Zhongying Chen ◽

Helen Zhou ◽

Hong Jin

Keyword(s):

Amino Acid ◽

Antibody Response ◽

Influenza A ◽

Amino Acid Substitutions ◽

Vaccine Production ◽

The Impact

Download Full-text

Could Environment Affect the Mutation of H1N1 Influenza Virus?

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17093092 ◽

2020 ◽

Vol 17 (9) ◽

pp. 3092

Author(s):

Dong Jiang ◽

Qian Wang ◽

Zhihua Bai ◽

Heyuan Qi ◽

Juncai Ma ◽

...

Keyword(s):

Influenza Virus ◽

Environmental Factors ◽

Social Development ◽

Influenza A ◽

H1n1 Influenza ◽

Influenza A Viruses ◽

Nighttime Light ◽

Complex Relationships ◽

The Impact ◽

The Relationship

H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000–2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.

Download Full-text

Development and evaluation of an M2-293FT cell-based flow cytometric assay for quantification of antibody response to native form of matrix protein 2 of influenza A viruses

Journal of Immunological Methods ◽

10.1016/j.jim.2011.04.010 ◽

2011 ◽

Vol 369 (1-2) ◽

pp. 115-124 ◽

Cited By ~ 9

Author(s):

Weimin Zhong ◽

Ju He ◽

Xiaoling Tang ◽

Feng Liu ◽

Xiuhua Lu ◽

...

Keyword(s):

Antibody Response ◽

Influenza A ◽

Matrix Protein ◽

Flow Cytometric Assay ◽

Influenza A Viruses ◽

Native Form ◽

Flow Cytometric ◽

293Ft Cell

Download Full-text

Systemic infection with highly pathogenic H5N8 of avian origin produces encephalitis and mortality in wild mammals at a UK rehabilitation centre

10.1101/2021.05.26.445666 ◽

2021 ◽

Author(s):

Tobias Floyd ◽

Ashley C Banyard ◽

Fabian ZX Lean ◽

Alexander MP Byrne ◽

Edward Fullick ◽

...

Keyword(s):

Avian Influenza ◽

Influenza A ◽

Wild Bird ◽

Influenza A Viruses ◽

Rehabilitation Centre ◽

Highly Pathogenic ◽

Wild Mammals ◽

Domestic Poultry ◽

Avian Origin ◽

The Impact

Europe has experienced extensive outbreaks of highly pathogenic avian influenza (HPAI) during the autumn/winter 2020/21 season. These avian influenza A viruses are highly transmissible and have infected over 1000 commercial and backyard poultry premises in Europe in this period causing high mortality. The impact on wild bird populations has also been significant, with over 400 detections in at least 47 different species reported across Europe as being positive with the H5N8 virus. Although different H5Nx combinations within the H5 clade 2.3.4.4b have been detected, the H5N8 subtype has predominated both in wild birds and domestic poultry outbreaks. In the UK there have been 22 outbreaks of H5N8 in domestic poultry and captive birds and more than 300 wild bird detections involving H5N8 over the autumn/winter 2020/21 period to April 2021. Here we detail the series of events surrounding the detection of an H5N8 influenza A virus of avian origin in five swans, a fox and three seals in a wildlife rehabilitation centre.

Download Full-text