TITERSAFE FOR EASY HEMAGGLUTINATION INHIBITION ASSAYS

Off-the-shelf reagent for influenza vaccine development

Critical virology reagents

20+ years virology expertise

Trusted by 100+ labs

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Get ready for easier influenza assays

When you need to grow live influenza virus for hemagglutination inhibition (HAI) assays, it means moving other key tasks to the back burner. It also means exposing team members to occupational health risks.

With TiterSafeTM, you can get straight to work testing immune sera. The first product of its kind, TiterSafe is an off-the shelf reagent that can easily substitute for live virus in your existing agglutination assays.

Free from the chore of growing virus stocks, your team will have more time to focus on important science. Plus, because TiterSafe is non-replicative, your lab team will be safer.

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TiterSafe consists of membrane-wrapped particles with a lentivirus core. Its hemagglutinin (HA) and neuraminidase (NA) surface proteins have amino acid sequences identical to those from specific strains of influenza A or influenza B virus. TiterSafe has many advantages over live influenza virus in HAI assays.

TiterSafe is a trademark of Integral Molecular.

Advantages

Ready-to-use, quality controlled reagent  
Non-replicative & safe for BSL-2 

Easy to substitute in your existing assays

Available for seasonal & custom strains 

“SARS-CoV-2 RVPs really helped us a lot since we did not have much previous expertise in SARS. The user meetings were especially helpful.”

TiterSafe Product Offerings

TiterSafe is available now for seasonal* and pandemic influenza strains. New TiterSafe products will be released as new seasonal and pandemic strains are announced.

* WHO-recommended strains for cell-based/recombinant vaccines

Catalog No.
Virus (Subtype)
Strain Information
HAP-1302
Influenza B (Victoria)
Austria/1359417/2021
HAP-1303
Influenza B (Yamagata)
Phuket/3073/2013
HAP-1205
Influenza A (H5N1)
Vietnam/1203/2004
HAP-1212
Influenza A (H3N2)
Darwin/6/2021
HAP-1213
Influenza A (H1N1)
Wisconsin/67/2022
HAP-1214
Influenza A (H5N1)
American Wigeon/SC/22-000345-001/2021 
HAP-1215
Influenza A (H3N2)
Massachusetts/18/2022
HAP-1216
Influenza A (H3N2)
Thailand/8/2022

Related product: Influenza Reporter Virus Particles (RVPs) for safe, easy neutralization assays are available with a GFP or luciferase reporter gene. Influenza RVPs are available in seasonal and pandemic strains; see the Reporter Virus Particle Catalog for details.

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What is TiterSafe?

TiterSafe is a flexible reagent that can be used in a variety of influenza assays, including HA, HAI, and NA ELLA assays.

TiterSafe is based on our highly validated platform for building pseudotyped Reporter Virus Particles. TiterSafe is produced in human cells using transfected DNA encoding the influenza HA and NA proteins. Its HA and NA surface proteins have amino acid sequences identical to those in live virus.

TiterSafe’s HA and NA surface proteins show the expected interactions and activities. In HAI assays with both sera and MAbs, TiterSafe shows the expected specificity for strain and lineage.

Because TiterSafe is not amplified by replication, the HA on the surface is the same on every particle and in every tube of reagent. Unlike with live virus, there is no sequence drift.

Due to its modular design, TiterSafe is flexible and highly customizable. By swapping out the DNA sequences, we can quickly and easily make TiterSafe product lines for new and custom influenza strains.

Results form HAI assay using TiterSafe strains and serum samples. Two-fold serum dilutions range from 1:8 to 1:16,384. Sera include A/Victoria, A/Darwin, B/Phuket, and B/Austria. Titer strains include A/Darwin and B/Phuket. A no TiterSafe control is included. Sera show the greatest inhibition against matched TiterSafe strains.
In sera and antibody screening, TiterSafe shows the expected specificity for strain and lineage.

How TiterSafe Replaces Live Influenza Virus

In HA and HAI assays, TiterSafe performs like live influenza virus by cross-linking red blood cells (RBCs). This cross-linked matrix is visible to the eye as a broad red area spread across the sample well. In the absence of cross-linking, or agglutination, the RBCs form a concentrated spot at the bottom of the well.

As with live virus, you can use TiterSafe to detect agglutination-inhibiting antibodies in vaccine sera, and thus estimate the level of protection against influenza virus. When specific antibodies bind to TiterSafe surface proteins, they block agglutination, and the RBCs form a concentrated spot.

TiterSafe is an easy and safe substitute. It fits into conventional HAI workflows as a straight replacement for live influenza virus. It provides accurate HAI assay results, ensuring that your research remains reliable and valid.

Because TiterSafe has a much better safety profile than live influenza virus, it can be easier to work with. It is non-replicative and safe in a BSL-2 environment.

TiterSafe produces easy-to-read results in HAI assays.

Resources

To hear our customers describe how they have used TiterSafe, view the webinar Innovative Research Tools to Combat Biological Threats

Visit the Resources page for more webinars, publications, and case studies featuring additional virology products and services.

Frequently Asked Questions

Wasted time is wasted money. Growing enough live influenza to conduct HAI assays for all samples in a phase III clinical trial can cost $600,000 to $1,000,000 per strain. This estimate includes the cost of your time, your team’s time, support staff, reagents, and materials. TiterSafe is priced affordably, and it frees up your team’s time to focus on other important work.
No, there is no gene packaged inside the particles. This feature minimizes the risk of TiterSafe facilitating the integration of genetic material into any genome.
TiterSafe can substitute in HAI assays not only for live influenza virus, but also for attenuated and inactivated influenza virus. Because some attenuated strains have modified HA sequences, TiterSafe may be even more representative of live virus than available attenuated technology. Unlike attenuated strains, TiterSafe eliminates the risk of infection.

Because strains can behave differently in the lab, it’s difficult to put a timeline on the development of new products. However, we can produce TiterSafe as fast as or faster than live virus. We aim to have new TiterSafe seasonal influenza strains available within 8-10 weeks of the seasonal strain sequence releases for the recommended Northern and Southern hemisphere strains.

Keep in mind that TiterSafe is concentrated and ready to use. That means that once TiterSafe arrives in your hands, you can start work in lab. There is no growing of banking of virus required.

TiterSafe is similar to Influenza Reporter Virus Particles (RVPs), but it lacks a reporter gene, and it is more concentrated.

Due to the similarities between the platforms we use to make the two products, we can provide matched reagents with the same surface proteins and overall structure: RVPs for neutralization assays, and TiterSafe for HAI assays.

Yes! Please contact us to learn more about ordering TiterSafe strains with the influenza surface protein variations of your choice.

While the concentration does vary somewhat between lots and product lines, TiterSafe always has sufficient titer to replace live virus in assays. Each tube of product meets the following minimum specifications:

  • The dilution for 1 HA unit is at least 1:256.
  • Each tube contains at least enough product for 1 HA plate (25uL) and 3 HAI plates using our recommended protocol.

Lot characteristics and recommended input volumes are included with product shipments.

For example product sheets and protocols, please contact us.

Scientists at Integral Molecular have used TiterSafe in ELLA assays to characterize the activity of antibodies against influenza neuraminidase. Full support for this application including protocols and sample data is coming soon. For ELLA applications, we recommend reaching out about custom TiterSafe since for best ELLA results you may need a custom mismatch HA and NA.

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