BTI, Home of the HighFive™ Cell Lines

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Find out why the HighFive cell lines are a popular tool for protein production

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Read some of the most relevant articles

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Use the original HighFive cell line or virus-free sub-clones

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The HighFive cell line was originally developed at BTI

Choose  HighFive

HighFive cells represent a safe, effective and inexpensive platform for protein production.

Indeed, their remarkable ability to produce very large amounts of recombinant proteins – such as diagnostic reagents and recombinant vaccines – remains unmatched.

The HighFive cells were originaly isolated from insects in BTI’s Granados lab in the late 1980’s.

Virus-free sub-clones of the original HighFive cells can be obtained from BTI or commercial partners for testing for non-commercial use, and affordable and flexible commercial licenses can be obtained from BTI.

 A tested platform for protein production

  • Hundreds of labs around the world use these cells.
  • HighFive cell lines were used to produce an FDA-approved human vaccine. Additional human and animal vaccines expressed in HighFive cells or virus-free sub-clones are currently at various stages of the regulatory approval process.

Safety first

  • HighFive cells are not known to potentially host any human pathogens.

Virus-free sub-clones

  • The original HighFive cells were found to host a non-pathogenic nodavirus. BTI researchers have developed several sub-clones that are virus-free and available for licensing.

True scalability with unmatched yields

  • The baculovirus expression vector system (BEVS) in insect cells offers highly scalable and inexpensive protein production. HighFive cells and sub-clones have been reported to produce 2-10x high levels of recombinant proteins compared to Sf9/Sf21 insect cells.

Proteins with less contaminants

  • When considering BEVS for protein expression, Sf9/Sf21 produce very high titers of baculoviruses. That can represent a major drawback during protein purification. Purifying proteins produced in HighFive cells is preferable, with as much as 100-fold less baculovirus produced.

Affordable licensing with peace of mind

  • BTI is the sole proprietor of HighFive cells and related sub-clones.

Available Cell Lines

All listed cell lines are the property of BTI.
All listed cell lines are available for Research Use Only under MTA and for commercial licensing.
Please contact the BTI Technology Transfer Office.

Cell Line Description Available from
HighFive-VF HighFive sub-clone free of alphanodavirus BTI
Tnao38 HighFive sub-clone free of alphanodavirus BTI
Tnms42 HighFive sub-clone free of alphanodavirus BTI
HighFive Original BTI-TN-5B1-4 cell line Thermo Fisher
Tnms42-sf Tnms42 sub-clone adapted to serum-free medium Acib*/BOKU University** (contact BTI)

* Austrian Centre of Industrial Biotechnology
** University of Natural Resources and Life Sciences, Vienna

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In the Literature

Baculovirus Expression Vactor System (BEVS)

First described in 1983, recombinant protein production in insect cells using BEVS, the technology has been used to produce thousands of proteins. The technology will continue to play a major role in our fight against emerging diseases.

Baculovirus-free methods using transient plasmid-based expression or stable transformation are well documented.
Transient or stable expression can be combined with infection using a non-recombinant “wild-type” baculovirus , to increase protein expression by transactivation.

Virus-free cell lines
The issue of adventious viruses in insect cell lines was recently reviewed. Trichoplusia ni cells are sucesptible to alphanodaviruses, but “unlike rhabdoviruses, alphanodaviruses are not generally considered to be mammalian pathogens”

First description of a virus-free sub-clone of HighFive cells:

The cell line, first believed to be from Ascalapha odorata (Ao38), was later identified as a Trichoplusia ni cell line and subl-clone of HighFive that emerged from a primary culture of A. odorata. It was renamed Tnao38. Erratum:

Protein glycosylation using BTI cell lines
The production of mammalianized glycoproteins in HighFive and Tnao38 cells can be achieved using the SweetBacTM approach

HighFive History

BTI, home of the HighFive cell lines.

Dr. Robert Granados was looking for ways to defend crops from the Cabbage Looper. During his research he made an unexpected discovery. The HighFive cell line and newer sub-clones free of nodavirus are a popular tool for recombinant protein production.

BTI is the exclusive owner of the proprietary HighFive cell line and related sub-clones. Contact us to inquire about cell lines available for testing and request commercial-use licenses

Most people who encounter the cabbage looper, a green caterpillar pest that dines on vegetable crops, would call it a pest and leave it at that. But thanks in part to research at BTI, these humble garden nuisances have transcended their bad reputation by helping lead to the creation of a life-saving vaccine.

This unlikely connection came about thanks to insect virologist and BTI (now) Emeritus scientist Bob Granados, who was working at the time on developing genetically-engineered baculoviruses–a specific family of rod-shaped viruses that typically infect invertebrates–for biocontrol of insect pests in crops. In order to grow the viruses, Granados needed a reliable host. By 1994, he settled on none other than the cabbage looper–using cells from the insect as virus incubators. These cells were so effective at producing the key proteins necessary for biocontrol research, the line was patented, and became a standard tool in the Granados and other research labs–nicknamed the “High Five” cell line.

Prior to this work, medical researchers began to investigate the feasibility of developing vaccines for Human Papilloma Virus (HPV), the most common sexually-transmitted disease that infects 14 million people every year. With persistent infection, the virus can lead to cervical and other cancers.

Scientists looked into using baculoviruses as a safe method for engineering HPV-neutralizing antigens which could be given as a vaccine. And, like Granados, they needed a stable host cell to grow their engineered baculoviruses in. “A lot of labs were looking for a good insect line to do this work,” said Paul Debbie, Director of Research and Director of New Business Development. “They needed it to be stable, and able to produce a lot of protein–so Bob did some work to see if the High Five cell line could work for this, and it was.”

Through research collaborations with scientists at other universities and institutes, and through partnering with drug development companies MedImmune and GlaxoSmithkline, Granados’ High Five cabbage looper cell line became the vehicle for producing the HPV vaccine known as Cervarix, one of the only two HPV vaccines available today.

Debbie says that this achievement would never have been possible without the diligent scientific research done by Granados and his counterparts. “There were all these basic science projects converging to one very useful therapeutic that saves lives,” said Debbie. “With basic research, one doesn’t necessarily know what the final outcome is going to be–it takes this very circuitous route, and it can end up having a big impact.”


For licensing inquires contact

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Julien Fey

Director of Technology Transfer


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Kelli Monce

Technology Transfer Specialist

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Paul Debbie

Director of Research, Director of New Business Development



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