Influenza: Immunodetection and vaccine development

Influenza (also known as flu) is an acute respiratory illness caused by the influenza viruses A, B, C and D. Amongst them, influenza A, B and C affect humans (Table 1).

Table 1. Classification of Influenza Virus. Source: Sino Biological Inc.

  Influenza A Influenza B Influenza C
Hosts Humans, waterfowl, poultry, pigs, horses, sea mammals, bats Humans, seals Humans, pigs, dogs
Gene Segments 8 8 7
Proteins 11 11 9
Clinical Features Moderate to severe illness Milder disease than Influenza A Largely subclinical
Epidemiological Features Causes pandemics Less severe epidemics than Influenza A; no pandemics Does not cause epidemics or pandemics

 

Influenza A and B viruses exhibit the potential to cause epidemic (interpandemic or seasonal) influenza, and influenza A viruses can also be responsible for pandemics.

Influenza virus structure

Influenza A viruses consist of eight negative-sense, single-stranded viral RNA (vRNA) gene segments that encode 10 viral proteins (Figure 1).

Diagram of Influenza Virus.Figure 1. Diagram of Influenza Virus. Image Credit: Sino Biological Inc.

With the help of the nucleoprotein (NP), the eight genome segments are encapsulated loosely. Polymerase complexes consisting of three polymerase proteins, PB1, PB2 and PA, are situated at the ends of nucleocapsids.

Such helical capsids have been encircled by the matrix protein 1 (M1) and a host-derived lipid bilayer envelope in which the viral surface glycoprotein hemagglutinin (HA), the matrix protein 2 (M2) and neuraminidase (NA) are embedded.

HA, NA and NP are known as the three significant antigens of the influenza virus, which play crucial roles in the lifecycle of a virus (Table 2). Their recombinant proteins find extensive use in fundamental research, vaccine development, therapeutics and diagnosis.

Table 2. Classification of Influenza Virus. Source: Sino Biological Inc.

Antigens Functions in Lifecycle Applications
HA Binding to sialic acid receptors on the surface of the host cell membrane, helping the interfusion of the viral envelope with the host cell membrane. Basic research; Vaccine development; Anti-hemagglutinin antibody development; Detection reagents development
NA Mediating the release of nascent viral particles assembled in the host cells by cleaving sialic acid groups from glycoproteins. Antiviral drug development; Basic Research; Vaccine development; Antibody development; Detection reagents development
NP A major component of the ribonucleoprotein complex, engaging in viral gene replication, transcription, and translation. Antiviral drug development; Basic Research; Antibody development; Detection reagents development

 

Influenza pandemics and strains

In the past, influenza pandemics were caused by the influenza A viruses. This could be additionally divided into different subtypes based on HA and NA differences.

Four influenza pandemics happened in the past 10 decades: the H1N1 Spanish flu pandemic (1918–1920), the H2N2 Asian influenza pandemic (1957–1958), the H3N2 Hong Kong flu pandemic (1968–1969), and the H1N1/09 swine flu pandemic (2009–2010) (Table 3).

Table 3. Four Influenza Pandemics in the Past 100 Years. Source: https://en.wikipedia.org/wiki/Influenza_pandemic

Name Date Subtype Infected (est.) Deaths Case Fatality Rate
Spanish Flu 1918-1920 H1N1 500 million or >1 billion 17–100million 2–3%, or ~4%, or ~10%
Asian Flu 1957-1958 H2N2 >500 million 1–4 million <0.2%
Hong Kong Flu 1968-1969 H3N2 >500 million 1–4 million <0.2%
Swine Flu 2009-2010 H1N1/09 0.7–1.4 billion 151,700–575,400 0.01%

 

The strains accountable for the four pandemics, H1N1 (swine flu and Spanish flu), H2N2 (Asian flu), and H3N2 (Hong Kong flu), have gained increased attention. In the last two decades, several potential pandemic strains have appeared with various zoonotic influenza events (Figure 2).

Emerging Potential Pandemic Strains in the Last 20 Years.Figure 2. Emerging Potential Pandemic Strains in the Last 20 Years. Image Credit: Sino Biological Inc.

Sino Biological has come up with a panel of antigen proteins and antibodies for influenza pandemic strains (Table 4). It has been designed to be utilized for numerous biochemical assays, like antigen detection, antibody titer and antigenic characterization assays.

Table 4. Influenza Pandemic Strains. Source: Sino Biological Inc.

Subtype Strain Year Antigen Proteins Antigen Antibodies
H1N1 A/Brevig Mission/1/1918 1918 HA, HA1, M1, NP HA
H1N1 A/California/04/2009 2009 HA, HA0, HA1, NA HA, NA
H2N2 A/Guiyang/1/1957 1957 HA, HA1  
H3N2 A/Hong Kong/1/1968 1968 HA, HA1, NP NP
H5N1 A/Hong Kong/483/97 1997 HA, HA1 HA
H7N7 A/Netherlands/219/2003 2003 HA, HA1, NA HA, NA
H7N9 A/Shanghai/1/2013 2013 HA, HA1, HA1+HA2, NA, NP HA
H9N2 A/Hong Kong/35820/2009 2009 HA, HA1  

 

Flu prevention and control

Early diagnosis and vaccination are significant methods to avoid and control the flu. Early diagnosis and treatment can efficiently reduce the duration of the illness, relieve symptoms and regulate the spread of the virus. The World Health Organization (WHO) suggests annual vaccination to prevent seasonal influenza.

Immunodetection

A common method used to diagnose flu is Immunodetection. Antibodies that target NP proteins are generally utilized for immunodetection in different assays. This includes lateral flow assay, enzyme-linked immunosorbent assay and direct fluorescent antibody tests.

As a result of the high frequency of antigenic drift or shift present in several influenza strains, broad-spectrum influenza antibodies are preferred specifically for diagnosing flu. Sino Biological has determined six pan-antibody pairs each against the NP protein of influenza A and B (Table 5).

Table 5. Pan Antibody Pairs for NP Detection. Source: Sino Biological Inc.

Pair No. Capture Ab Detection Ab Pair No. Capture Ab Detection Ab
PanA-1 40205-MM16 40208-R014 PanB-1 40438-R004 40438-MM10
PanA-2 40205-R063 40205-MM18 PanB-2 40438-R036 40438-MM10
PanA-3 40208-R117 40205-MM18 PanB-3 40438-MM05 40438-R036

 

Such matched pairs have the ability to detect broad-spectrum strains inside the target subtype in the absence of any cross-reactivity along with other subtypes (Figure 3).

Six Pan antibody pairs each against the NP protein can detect different NP proteins of influenza A or B virus by ELISA assay.Figure 3. Six Pan antibody pairs each against the NP protein can detect different NP proteins of influenza A or B virus by ELISA assay. Image Credit: Sino Biological Inc.

Vaccine development

Flu, particularly seasonal flu, is a universal threat to human health. Vaccination is an efficient method to avoid the spread of infection. Annually, numerous different flu strains are chosen as vaccine strains depending on the surveillance data of the recent isolates and their performance in the early season.

Over the last few years, the majority of the vaccines are either trivalent or quadrivalent, such as one H1N1, one H3N2 and Yamagata and/or Victoria-type flu B.

Sino Biological has liberated a panel of recombinant antigen products spanning all WHO-recommended vaccine strains in recent years (Table 6). The products include NA, HA, as well as NP and have been developed for vaccine development.

Table 6. Antigens for 2015-2022 Vaccine Strains. Source: Sino Biological Inc.

Strains HA NA NP Year
A/Brisbane/02/2018 (H1N1) 40719-V08H 40767-V08B 40776-V08B 2019-2020
A/California/7/2009 (H1N1) 11085-V08B   40205-V08B 2016-2017, 2015-2016
A/Cambodia/e0826360/2020 (H3N2) 40789-V08H
40789-V08H1
40784-V08B 40778-V08B 2021-2022
A/Guangdong-Maonan/SWL1536/2019 (H1N1) 40717-V08H   40723-V08B 2020-2021
A/Hawaii/70/2019 (H1N1) 40717-V08H   40724-V08B 2020-2021
A/Hong Kong/2671/2019 (H3N2) 40721-V08H   40753-V08B 2020-2021
A/Hong Kong/45/2019 (H3N2) 40765-V08H   40754-V08B 2020-2021
A/Hong Kong/4801/2014 (H3N2) 40555-V08B 40569-V08B 40781-V08B 2017-2018, 2016-2017
A/Kansas/14/2017 (H3N2) 40720-V08H 40766-V08B 40779-V08B 2019-2020
A/Michigan/45/2015 (H1N1) 40567-V08H1 40568-V08B 40777-V08B 2018-2019, 2017-2018
A/Singapore/INFIMH-16-0019/2016 (H3N2) 40580-V08H   40779-V08B 2018-2019
A/Switzerland/9715293/2013 (H3N2) 40497-V08B   40499-V08B 2015-2016
A/Victoria/2570/2019 (H1N1) 40787-V08H
40787-V08H1
40785-V08B 40774-V08B 2021-2022
A/Wisconsin/588/2019 (H1N1) 40787-V08H
40787-V08H1
40785-V08B 40774-V08B 2021-2022
B/Brisbane/60/2008 40016-V08B 40203-VNAHC 40783-V08B 2017-2018, 2016-2017, 2015-2016
B/Colorado/06/2017 40581-V08H   40782-V08B 2019-2020, 2018-2019
B/Phuket/3073/2013 40498-V08B 40502-V07B 40500-V08B 2021-2022, 2020-2021, 2019-2020, 2018-2019, 2017-2018, 2016-2017, 2015-2016
B/Washington/02/2019 40722-V08H 40790-V08B 40755-V08B 2021-2022, 2020-2021

 

Summary

Regardless of the ongoing coronavirus disease 2019 pandemic, influenza occurs every year. This leads to substantial mortality and morbidity. Several relevant studies are in progress to help control the influenza virus.

The sophisticated tools designed by Sino Biological consist of a library of antiviral antibodies and a huge collection of recombinant virus proteins. Such reagents could be utilized extensively for vaccine development and immunodetection for the influenza virus.

About Sino Biological Inc.

Sino Biological is an international reagent supplier and service provider. The company specializes in recombinant protein production and antibody development. All of Sino Biological's products are independently developed and produced, including recombinant proteins, antibodies and cDNA clones. Sino Biological is the researchers' one-stop technical services shop for the advanced technology platforms they need to make advancements. In addition, Sino Biological offers pharmaceutical companies and biotechnology firms pre-clinical production technology services for hundreds of monoclonal antibody drug candidates.

Sino Biological's core business

Sino Biological is committed to providing high-quality recombinant protein and antibody reagents and to being a one-stop technical services shop for life science researchers around the world. All of our products are independently developed and produced. In addition, we offer pharmaceutical companies and biotechnology firms pre-clinical production technology services for hundreds of monoclonal antibody drug candidates. Our product quality control indicators meet rigorous requirements for clinical use samples. It takes only a few weeks for us to produce 1 to 30 grams of purified monoclonal antibody from gene sequencing.


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Last updated: Mar 23, 2022 at 6:49 AM

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