Advances in influenza research

Thought LeadersDr. Mohammad SafiarianAssociate Product ManagerSino Biological

This interview with Dr. Mohammad S Safiarian, Associate Product Manager at Sino Biological, discusses the advances in influenza research and how effective vaccines are developed.

Could you introduce yourself and describe your primary areas of work?

I am Dr. Mohammad Safiarian, the Associate Product Manager at Sino Biological. In my role, I am responsible for developing and marketing protein products. I obtained my Ph.D. in biochemistry from Georgia State University and completed my postdoc at the Georgia Institute of Technology and Baylor College of Medicine.

My expertise primarily concerns protein science, DNA biochemistry, and enzymology. Throughout my career, I have authored several peer-reviewed papers that have garnered over a hundred citations.

What are the key aspects of combating influenza, and how do diagnostic tools contribute to timely intervention?

Accurate diagnosis, effective prevention, and appropriate treatment are vital in combating influenza. Diagnosing influenza involves various methods, including antigen detection, virus isolation, RT-PCR, immuno/fluorescence assays, and rapid molecular assays.

These diagnostic tools help healthcare professionals identify the presence of influenza viruses and determine the specific viral strains causing the infection. Accurate diagnosis is crucial for timely intervention and appropriate management. Prevention is undoubtedly the most effective approach to combat influenza.

Vaccination remains the cornerstone of influenza prevention, and influenza vaccines are designed to stimulate the immune system to produce antibodies that recognize and neutralize the specific strains of the virus.

Can you provide an overview of the influenza virus’s structure and how it affects diagnosis and vaccine development?

Influenza viruses have a unique structure. Hemagglutinin (HA) is a glycoprotein on the surface of the influenza virus. It plays a crucial role in viral entry into host cells by binding to receptors on the surface of respiratory cells. It is a primary target for neutralizing antibodies induced by influenza vaccines and antiviral drugs.

Neuraminidase (NA) is another surface glycoprotein that facilitates the release of newly formed virus particles from infected cells. It targets antiviral medications and can also be utilized in vaccine development.

Nuclear protein (NP) forms the backbone of the viral particle and is involved in viral replication and packaging of the viral genome. NP is a conserved antigen and is most commonly utilized in diagnostic tests to detect the presence of influenza viruses.

Matrix protein two (M2) is a transmembrane protein in viral assembly and release. It is a target of antiviral drugs, and certain influenza vaccines contain M2 antigens to elicit immune responses.

Non-structural protein one, or NS1, is a multifunctional protein that helps the virus evade the host's immune response. It is not a target for current influenza vaccines, but it plays a role in diagnostic tests to differentiate between influenza virus subtypes.

The influenza virus has three polymerase proteins, PB1, PB2, and PA, essential for virus replication and transcription. These proteins are involved in adapting influenza viruses to new hosts and are targets of new antiviral drugs.

The development and application of influenza vaccines have played a pivotal role in our ongoing fight against this ever-changing viral infection.

The World Health Organization (WHO) plays a critical role in monitoring and responding to the global threat of influenza. Through its Global Influenza Surveillance and Response System (GISRS), the WHO closely monitors the spread and evolution of flu viruses worldwide.

Based on its comprehensive surveillance data, the WHO, in collaboration with experts from various countries, makes annual recommendations for the strains to be included in the seasonal influenza vaccines. These recommendations, communicated through the WHO global influenza updates and consultation meetings, guide vaccine manufacturers in formulating the most appropriate vaccine composition for the upcoming flu season.

What methods are currently being used for the manufacture of the influenza vaccine?

Two primary technologies are used for influenza vaccine production: egg-based and recombinant methods. Egg-based vaccines have been the traditional method of influenza vaccine production for decades. They involve growing influenza viruses in chicken eggs, a well-established and relatively affordable process.

The egg-based approach allows for larger-scale production of vaccines to meet the demand during the flu season. However, it does have some drawbacks. Firstly, the production is time-consuming, taking approximately eight months from strain selection to vaccine availability.

This lag time may pose challenges in rapidly responding to emerging antigens or pandemics. Additionally, some individuals may have allergies to egg proteins, limiting the suitability of egg-based vaccines for these individuals.

On the other hand, recombinant flu vaccines represent a newer technology that does not rely on eggs for production. Recombinant vaccines are developed using genetic engineering techniques, where specific proteins from the influenza virus are expressed in other cell types, such as mammalian or insect cells. This method offers several advantages.

Firstly, recombinant vaccines can be produced relatively quickly, taking around five months from strain selection to vaccine availability. Moreover, recombinant vaccines suit individuals with egg allergies since no eggs are involved in the production. However, there are some drawbacks associated with recombinant vaccines.

For example, they can be more expensive than egg-based vaccines, primarily due to the cost of the cell culture system and associated technology. As a newer technology, recombinant vaccines may have limited long-term efficacy data. Both approaches remain valuable in ensuring a sufficient supply of influenza vaccines to protect populations worldwide.

What types of flu vaccines are commonly used today?

A wide range of formulations and technologies are employed to combat this ever-evolving viral infection, influenza, including the live attenuated influenza vaccine (LAIV), which consists of weakened viral strains. While these strains can still infect and replicate within the body, they are designed to cause only mild or no symptoms.

This vaccine is typically administered as a nasal spray and has been approved for use in certain age groups. The advantages include a single dose and strong and long-lasting immunity, and the disadvantage is that it is not recommended for immunocompromised individuals.

The second technology is inactivated influenza vaccines, produced by growing the virus in eggs and then inactivating them using chemicals. This process ensures that the virus is no longer capable of causing disease. Inactivated vaccines contain viral components such as hemagglutinin and neuraminidase proteins.

Adjuvants, which enhance the immune response, are often added to improve the vaccine's effectiveness. The advantages of these types of vaccines are that they are safe for all ages, and the disadvantages include the requirement for adjuvants and the potential need for multiple doses.

The third technology is virosomal vaccines, which utilize reconstituted virus envelopes containing HA, NA, and lipids. These vaccines do not contain the entire virus but focus on essential viral components.

The virosomes facilitate the delivery of the components into the immune system and stimulate the immune response against the influenza virus. The advantages of this type are that they are safe and provide an excellent immune response. However, they can be expensive and may require multiple doses.

Split-virion is the fourth type of influenza vaccine, which involves the inactivation of the virus followed by the splitting of the virus into its components. These components are then purified, ensuring that only specific viral antigens, such as HA or NA, are present in the vaccine.

Split-virion vaccines induce an immune response against these viral components, protecting against the corresponding influenza strain.

The advantage of split-virion vaccines includes providing an excellent immune response, and the disadvantage is that they may not cover all strains and require adjuvants.

Lastly, subunit vaccines utilize purified HA or NA proteins from the influenza virus. These proteins, the major antigens responsible for stimulating the immune response, are combined with adjuvants to enhance the immune response.

Subunit vaccines offer targeted protection against specific strains of influenza. The advantage of this type of vaccine is that they are safe (as they no longer contain live viruses). However, there is a potential need for multiple doses, which provide a weaker immune response than others.

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What are some exciting directions for the future of influenza vaccine development?

As we continue to combat influenza and strive for more effective prevention strategies, ongoing research and innovation in vaccine development pave the way for future advancements.

In the continuous battle against influenza, scientists and researchers are constantly exploring innovative approaches to improve the selection of seasonal flu strains for vaccine development. Traditional serological methods, which involve testing blood samples for the presence of antibodies, can be labor-intensive and inconsistent.

However, with advancements in bioinformatics and computational tools, we now have new avenues to anticipate and track the natural evolution of flu viruses. One such tool is Nextflu, an online platform that utilizes bioinformatics to visualize the genetic evolution of seasonal flu viruses.

By analyzing the genetic sequences of flu viruses obtained from surveillance data, Nextflu can provide insights into how these viruses evolve and change over time. This information is crucial for predicting the most likely strains to circulate in upcoming flu seasons, allowing researchers to make informed decisions regarding vaccine composition.

Another valuable tool in the selection of seasonal flu strains is antigenic cartography. This tool utilizes the surveillance data provided by the World Health Organization to analyze the antigenic properties of flu viruses. By plotting the antigenic relationships between different strains on the map, researchers can identify clusters of viruses with similar antigenic characteristics. This information helps in understanding how flu viruses evolve and how they may respond to immune pressure, guiding the selection of strains for vaccine formulation.

Researchers strive to develop a universal flu shot that provides broad and durable protection against multiple influenza strains by targeting viral components, including the HA Stalk Domain, NP, and NA. These approaches focus on conserved regions of the virus, which have the potential to induce immune responses capable of recognizing and neutralizing a wide range of influenza viruses. One key viral target is the HA Stalk Domain. This region of the HA protein plays a crucial role in cell membrane fusion, allowing the virus to enter the host cell.

Compared to the highly variable head domain, the stem domain of the HA stalk is relatively conserved across different influenza strains. Researchers aim to induce immune responses that can neutralize a wide range of influenza viruses by targeting the HA Stalk Domain.

Another promising target is Matrix Protein 2, or M2. M2 is highly conserved among different influenza strains, making it an attractive target for universal vaccines. The nuclear protein (NP) of the influenza virus is also an attractive target for a universal vaccine as it is involved in viral replication and highly conserved across different strains. The influenza virus's neuraminidase (NA) protein has been identified as a potential target for universal vaccine development.

Scientists have explored various platforms that offer innovative approaches to vaccine development. One such platform is the Virus-Like Particle (VLP) which involves the co-expression of the HA, NA, and M genes together, generating VLPs resembling the influenza virus structure. VLPs mimic the native virus without the genetic material, making them safe for use in a vaccine.

By presenting the viral antigens in a highly organized and immunogenic manner, VLP-based vaccines can elicit strong immune responses. Another platform is nanoparticles. In this approach, the ferritin protein and HA of the influenza virus self-assemble into nanoparticles. These nanoparticles display the viral antigens in a highly ordered and repetitive manner, enhancing their immunogenicity. By leveraging the self-assembly property of ferritin and HA, nanoparticle-based vaccines can induce robust and cross-reactive immune responses.

The viral vector platform utilizes an adenoviral vector to deliver the required antigen. Adenoviral genomic sequences are engineered to include a gene cassette encoding the desired viral antigens. When administered, the adenoviral vector delivers the antigenic genes into the host cell, stimulating the immune system to generate an immune response.

Nucleic acid-based platforms, such as DNA and mRNA vaccines, have also shown promise in universal flu vaccine development. A plasmid carrying the gene cassette encoding the desired immunogen is constructed in the DNA vaccine approach. The plasmid is then delivered into the host cell, allowing it to produce the viral antigen and trigger an immune response. Similarly, mRNA molecules representing the immunogen are formulated and delivered into the host cell in mRNA vaccines. Once inside the cell, the mRNA instructs the production of the viral antigen, initiating the immune response.

The pursuit of a universal influenza vaccine has gained significant momentum. As previously mentioned, these vaccine candidates utilize various platforms, including VLPs, nanoparticles, viral vectors, and nucleic acids. Several of these vaccine candidates are currently in various phases of clinical trials, including phases one through two.

What are some key hurdles in pursuing universal influenza vaccines, specifically in preclinical trials and evaluation criteria?

One major challenge lies in evaluating novel influenza vaccines during preclinical trials. Unlike seasonal influenza vaccines, which can rely on established endpoints such as antibody titers and seroconversion rates, universal vaccines target broader immune responses that extend beyond strain-specific antibodies.

There is a lack of uniform evaluation criteria for these novel vaccine candidates, making it challenging to compare their efficacy across different studies. Another obstacle in the development of universal vaccines is the absence of established correlates of protection for broadly cross-reactive immune responses.

Traditional measures of vaccine efficacy, such as neutralizing antibody titers, may not fully capture the effectiveness of a universal vaccine that aims to provide broad protection against diverse influenza strains. Furthermore, the funding landscape poses a significant challenge.

Despite the potential impact and importance of universal influenza vaccines, funding for their development is limited. Resources are often focused on seasonal influenza vaccine production and distribution, leaving a funding gap for research and development of universal vaccine strategies.

How has Sino Biological been involved in influenza vaccine development?

Sino Biological is dedicated to supporting and advancing the field of influenza vaccine research. As a globally leading biotechnology company, we offer a wide range of high-quality bioreagents that are instrumental in the development of influenza vaccines

Sino Biological offers comprehensive solutions for influenza vaccine development and production to vaccine manufacturers. We provide a wide range of influenza virus research reagents, including influenza vaccine antigens, antibody pairs, neutralizing antibodies, and kits. Additionally, we offer high-quality technical services such as kit development, antigen expression, and antibody development. These products and services are suitable for various vaccine development scenarios, such as candidate vaccine strain screening, virus seed batch preparation, vaccine safety, and immunogenicity assessment, and vaccine protective efficacy evaluation.

By utilizing Sino Biological's ProVir viral antigen collection, researchers can investigate and characterize the immune response induced by influenza vaccines, paving the way for developing more effective preventive strategies.

Influenza antibodies play important roles in vaccine development processes, including vaccine strain screening, seed lot quality control, and preclinical safety evaluation. Sino Biological has developed 200+ influenza antibody products, including pan HA/NP antibodies, pan NP antibody pairs, and neutralizing antibodies, covering various applications such as WB, ELISA, sandwich ELISA, HI, and MN, and providing comprehensive support for influenza vaccine development.

In antiviral therapy research and vaccine potency evaluation, cytokines including IFN-γ, IL-4, IL-6, and IL-2 are monitored to assess the cytokine storm triggered by viral infection. Sino Biological has a collection of human and mouse cytokine ELISA kits, each of which undergoes eight QC tests. Sino Biological also offers kit development services and conducts full methodological validation to ensure the validity and stability of the detection.

In addition to cytokine ELISA kits, Sino Biological also offers a panel of influenza HA/NP antigen detection kits for the accurate quantification of HA or NP content in samples to support influenza vaccine production and development.

Our CRO services are designed to support research and development needs across various fields, including influenza vaccine research. We offer various services, including recombinant protein expression, recombinant antibody production, monoclonal antibody development, and polyclonal antibody development.

Our commitment to quality is evident in our ISO certificates. These certifications reflect our dedication to maintaining rigorous quality management systems to ensure the consistency and reliability of our products and services. We are proud to see our products cited in over 10,000 publications as of September 2022, appearing in prestigious and high-impact journals. This recognition demonstrates researchers' trust and confidence in our reagents and services.

At Sino Biological, we have established a strong global presence with our headquarters in Beijing, China. In addition to our main office, we have strategically placed branches in various cities to serve our customers better. Our branches can be found in Guangzhou, Shanghai, Taizhou, and Suzhou within China, allowing us to cater to the diverse needs of researchers and scientists nationwide.

Sino Biological has expanded internationally with branches in Tokyo, Frankfurt, Pennsylvania, and Texas. These locations enable us to provide efficient and reliable support to our customers worldwide, ensuring the prompt delivery of high-quality bioreagents and comprehensive CRO services. We are a global network facilitating scientific advancements and collaborations across borders.

Can you provide an overview and features of ProVir® developed by Sino Biological?

Sino Biological, Inc. has launched ProVir®, the world's most extensive collection of recombinant viral antigens. This comprehensive collection comprises over 1000 products representing 90+ virus types/subtypes and 350+ strains.

The ProVir® product line offers a diverse selection of high-quality recombinant proteins produced in insect and mammalian cells. These products undergo rigorous testing to ensure their purity and bioactivity.

The ProVir® portfolio includes an exceptional coronavirus catalog, encompassing a vast array of antigens from more than 300 strains of influenza, as well as various other elusive viral proteins like RSV, Ebola, and Cytomegalovirus. These reagents are specifically designed to support vaccine research and drug development endeavors.

How can AI and recombinant technologies from Sino Biological be applied in influenza vaccine development?

Sino Biological and Ainnocence have established an AI-enabled platform for antibody affinity maturation. Powered by a self-evolving artificial intelligence engine, Ainnocence's SentinusAI® is transforming affinity maturation.

SentinusAI® effectively ranks up to 1010 antibody sequences based on their predicted affinity toward one or more antigens within a few days.

When combined with Sino Biological's high-throughput recombinant antibody development program, top candidates can be expressed recombinantly at a lower cost and shorter lead time, generating affinity data with a high hit rate of 15%.

Among the different types of influencer vaccines, which one is known to be more effective and most popular?

The effectiveness of influenza vaccines can vary greatly depending on factors such as circulating strains, population demographics, and individual health conditions. However, among the different types of influenza vaccines, inactivated vaccines have been widely used and are a popular choice among healthcare professionals. Inactivated vaccines contain killed influenza viruses and are available as injectable shots.

There is a long history of safe and effective use of inactivated vaccines in preventing influenza infections. Recently, these vaccines have been continuously improved to target specific strains and are recommended for different age groups, including children, adults, seniors, and pregnant women.

It is important to note that the effectiveness of these influenza vaccines can be significantly influenced by various factors, as mentioned earlier, such as vaccine coverage, public health campaigns, and regional preferences. Consequently, healthcare professionals in different regions may recommend inactivated or live attenuated virus vaccines.

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How do researchers and companies ensure that seasonal flu vaccines are safe and effective when they are usually developed within a relatively short timeframe each year?

Vaccine developers need to prioritize safety. They conduct thorough preclinical and clinical studies to evaluate potential side effects. This usually involves extensive testing in animal models for preclinical studies and multiple phases of clinical trials in humans. They also monitor the long-term safety and effectiveness, typically after the vaccine is marketed.

Secondly, vaccine efficacy is another critical factor. The vaccine has to work and developers must select appropriate antigens targeting the most prevalent and virulent strains of influenza. Vaccine developers continuously monitor and analyze circulating strains to identify the most suitable candidates for inclusion in their annual vaccines.

Optimizing the manufacturing processes is also essential to ensure the timely delivery of vaccines to healthcare professionals without compromising quality. This factor ensures rapid production and distribution. Streamlining regulatory processes is another consideration. In many countries, regulatory bodies collaborate with vaccine developers to streamline these processes, ensuring vaccines reach the market or healthcare professionals promptly. This can expedite vaccine development while maintaining rigorous standards.

Finally, ongoing vaccine effectiveness monitoring and evaluation in the post-marketing stage are crucial. Post-marketing surveillance helps identify any potential rare adverse events or changes in virus circulation that may impact vaccine performance.

Are antibodies against influenza used only for diagnostic purposes, or do they also have applications in treating influenza?

The antibodies against influenza can be utilized for both diagnostic and treatment purposes. In terms of diagnosis, antibodies are employed in various tests, such as rapid diagnostic tests in clinics and serological assays in laboratories, to identify the presence of the influenza virus or influenza-specific antibodies in patient samples.

These tests are highly beneficial for healthcare teams in confirming the occurrence of influenza infection in patients. Regarding treatment, specific monoclonal antibodies have been developed to address influenza. These antibodies target and neutralize the influenza virus, reducing viral replication and the severity of symptoms.

They bind to specific viral components inhibiting the virus from entering and infecting host cells. These antibodies can be administered as therapeutic options for specific groups of individuals, such as those at higher risk of experiencing severe influenza symptoms due to underlying conditions or compromised immune systems. However, it is essential to note that these antibody-based treatments are typically specific to certain strains or subtypes of influenza, and they do not generally offer broad protection against all influenza viruses. Therefore, this remains a limited option.

Is there currently a universal vaccine available?

As of now, there is no universally approved influenza vaccine available. However, extensive research is underway to develop a universal vaccine that can provide long-lasting and broad protection against multiple strains of influenza. Several vaccine candidates are currently being investigated in preclinical and clinical trials, showing promising results. Ongoing research efforts are focused on overcoming the challenges of developing an effective universal vaccine for global use.

One major obstacle is the lack of a uniform evaluation framework for novel influenza vaccines during preclinical trials. In other words, standardized methods for assessing the efficacy and immune response generated by these vaccines are still being developed.

Another challenge is the limited funding available for universal vaccine development. Vaccine research and development processes are costly, requiring extensive testing in clinical trials to ensure safety and effectiveness. Therefore, adequate funding is crucial for conducting robust studies and advancing potential vaccine candidates.

Where can readers find more information about Sino Biological?

To learn more about Sino Biological, please search www.sinobiological.com, to learn more about influenza vaccine development and production solutions by Sino Biological, please visit the website.

Dr. Mohammad Safiarian is the Associate Product Manager at SinoBiological, where he is responsible for product development and marketing of protein products. He earned his Ph.D. in Biochemistry from Georgia State University and completed post-doctoral training at the Georgia Institute of Technology and Baylor College of Medicine.

Dr. Safiarian's expertise lies in protein science, DNA biochemistry, and enzymology, and he has authored several peer-reviewed papers with over 100 citations.

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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Comments

  1. William CHUI William CHUI Hong Kong S.A.R. says:

    It seemed that the author intended to avoid mentioning mRNA influenza vaccine which is in
    Preclinical or Phase 1 clinical trial. As a scientist with credibility, he or she should provide neutral and unbiased information.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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