For generations, silkworm pupae were simply a byproduct of silk spinning. Today, the biotech spotlight is shifting to their dormant power: transforming these “waste” organisms into natural protein factories. Turns out, when silkworm pupae are harnessed as living bioreactors, they can produce complex recombinant proteins and vaccine antigens at a scale—and cost—that makes mammalian cell culture systems look cumbersome.

In this episode of the Smart Biotech Scientist Podcast, host David Brühlmann speaks with Masafumi Osawa, a global strategy leader at KAICO with an unconventional path into biotechnology. Originally trained in cultural anthropology, Masafumi’s career was shaped by hands-on experience in pharmaceutical business development across diverse markets.

Key Topics Discussed

• Silkworm-based biomanufacturing evolves from traditional silk production to modern vaccines and therapeutics.
• KAICO’s product pipeline advances stepwise from livestock vaccines toward regulated human biologics.
• Oral vaccine development highlights stress reduction, cost efficiency, and antigen-specific delivery advantages.
• Silkworm expression platform enables rapid vaccine development once DNA sequences become available.
• Regulatory pathways differ between human and animal health, requiring tailored, country-specific strategies.
• Future silkworm-based biologics expand beyond vaccines to antibodies, complex proteins, and rare diseases.
• High productivity and scalability of silkworm pupae outperform traditional biomanufacturing equipment in efficiency.
• Silkworms are reframed from agricultural byproducts into essential biotechnology tools inviting collaboration.

Episode Highlights

• Silkworm bioreactors: KAICO’s approach to expressing complex proteins, including oral and injectable vaccines for animals and clinical-stage human health products [00:40]
• Development pipeline overview: PCV2 oral vaccine for pigs (registered in Vietnam), companion animal products, and human norovirus vaccine entering Phase 1 trials [02:50]
• Advantages of silkworm-produced antigens for both injectable and oral vaccines, and comparison to plant-based systems [04:57]
• How silkworm production enables rapid scale-out and high-yield protein expression for global accessibility [05:34]
• Speed of vaccine development with the silkworm platform—example with SARS-CoV-2 recombinant protein produced in three months [08:08]
• Key regulatory differences between animal and human vaccine development, including country-specific classification and global harmonization efforts [09:14]
• Sustainability and distributed manufacturing potential of silkworm-based systems [11:10]
• Milestones toward the first human biologic produced in silkworms, with phase 1 trials starting soon [12:27]
• Protein yield per silkworm pupae—scalability advantages compared to conventional bioreactor approaches [14:04]
• Masafumi Osawa’s thoughts on the future of silkworm-based biologics: from democratized therapies to personalized medicines [15:15]

In Their Words

Silkworms were once used purely for producing silk, and their pupae were often considered waste. Today, those same silkworm pupae have the potential to address major global health challenges and offer new modalities for vaccines and therapeutic proteins. If any researchers listening today are struggling with difficult protein expression—whether it's a VLP, membrane protein, or complex antigen—I would be very happy to explore how we can support your R&D.

Episode Transcript: Silkworm Biomanufacturing: From Ancient Silk Production to Phase I Vaccine Trials - Part 2

David Brühlmann [00:00:36]:
Welcome back to Part Two with Masafumi Osawa from KAICO. In Part One, we explored how silkworm pupae function as natural bioreactors expressing complex proteins using a baculovirus expression system. Now we’re moving from platform science to product reality. KAICO isn’t just offering contract services—they’re developing injectable and oral vaccines for both human and animal health. We’ll examine their development pipeline, discuss the unique regulatory considerations when your bioreactor is alive, and explore where silkworm-based manufacturing fits into the future of biologics production. Let’s continue our conversation.

Let’s shift gear, Masa. Let’s focus on your product pipeline. What are the kind of molecules you're developing? How well advanced are you in these various molecules? I'm curious to see what you're working on right now.

Masafumi Osawa [00:02:50]:
Our pipeline is designed around a stepwise regulatory strategy, starting with segments that allow for rapid entry and progressing toward human applications after livestock validation. Our most advanced program is the PCV2 oral immunization product for pigs, registered in Vietnam as a functional feed additive. In real farm environments, it has shown performance comparable to injectable vaccines while substantially reducing labor and stress costs. This provides strong validation of oral antigen delivery using silkworm-derived proteins in livestock.

We are also developing oral vaccines for cats, including FPV (feline panleukopenia virus), FCV (feline calicivirus), and FHV-1 (feline herpesvirus type 1), and producing purified CPV (canine parvovirus) antigens for dogs. Our aim is to reduce vaccination stress in animals and offer alternatives to in-clinic injections, with implications for human health as well.

Our recombinant injectable human norovirus vaccine is preparing for Phase I clinical trials next summer under Japan’s AMED SCARDA program. This marks a major step toward establishing insect-based platforms in human pharmaceuticals. Beyond internal programs, we collaborate with partners to express complex proteins and antibodies, leveraging the unique capabilities of the silkworm system. Overall, our pipeline reflects a long-term progression from livestock to companion animals to human injectables and eventually oral medical vaccines for humans.

David Brühlmann [00:04:39]:
Oral vaccines are an exciting delivery approach because they reduce distress during administration. Are there specific antigen characteristics that work better—or worse—for oral vaccine applications, and where are the limits?

Masafumi Osawa [00:04:57]:
Silkworm-derived antigens offer significant advantages for both injectable and oral vaccines, although the reasons differ by modality. For injectable vaccines, the key strength lies in the ability to express antigens that are difficult or sometimes impossible to produce in other systems. This includes complex structural proteins and virus-like particles (VLPs), which often do not require mammalian-type N-linked glycosylation and therefore assemble particularly well in insect-based platforms.

The silkworm pupal environment provides a dense, multicellular physiological setting that naturally supports proper folding, multimerization, and high-yield expression. This is why we can obtain enough purified antigen from a single pupa to immunize several hundred pigs. When manufacturing injectable swine vaccines, this level of efficiency is extremely difficult to match with conventional cell culture systems.

For oral vaccines, the advantages are even more distinct. Previous plant-based oral vaccine approaches—such as rice or other edible crops—have struggled due to low expression levels or sharply increasing production costs at industrial scale. As a result, despite scientific interest, few plant-derived oral vaccines have reached commercial feasibility.

Silkworm pupae, however, function as naturally concentrated bioreactors, delivering expression levels far higher than those typically achieved in plants. At the same time, silkworms can be mass-produced at low cost, making them well suited for oral vaccine applications where dosage volumes are much larger than injectables. In our PCV2 oral program, for example, we formulate approximately 1.5 g per pig, accounting for variation in feed intake and ensuring sufficient mucosal exposure. By contrast, injectable formulations—with higher purity and potency—allow a single pupa to cover hundreds of animals.

Additionally, silkworm-based production avoids large bioreactors, extensive culture media, sterile water systems, and intensive cleaning operations. These factors significantly reduce manufacturing costs and environmental burden, giving our platform a strong economic advantage—particularly in vaccine applications where global accessibility and scalability are critical.

David Brühlmann [00:07:49]:
During the COVID pandemic, we heard over and over how important it is to be able to develop vaccines very quickly. I’m curious—using the silkworm platform, how fast can you develop a new vaccine? Is this comparable to, for instance, mRNA, or how does it differ?

Masafumi Osawa [00:08:08]:
As long as the DNA sequence is available, we can produce any kind of recombinant protein. That’s the first point. One example is that during COVID we also produced SARS-CoV-2 recombinant spike protein. It took just three months after the outbreak of COVID-19. I think that is one remarkable aspect of our platform.

David Brühlmann [00:08:32]:
That’s remarkable—very fast. And the advantage I see with your platform is that because you’re scaling out, it’s very easy to expand production rapidly and produce massive amounts of vaccines in a short time. On our podcast we usually focus on human medicine, so I’d like to take a quick deep dive into the animal side of things because that’s also very important. We often forget that there’s a huge market for animal health. What are the main regulatory differences between the two? Can you give us the two-minute version? Obviously, I'm sure there's a lot of more details, but what is the two minute version of the differences between human and animal health?

Masafumi Osawa [00:09:14]:
Regulatory pathways for silkworm-derived products differ significantly between human and animal health. Human vaccines follow globally harmonized standards, but because silkworm-derived antigens are unprecedented, we must work closely with Japan’s PMDA (Pharmaceuticals and Medical Devices Agency) to define raw material controls, GMP, CMC expectations, and quality control frameworks.

In the animal health sector, pathways differ by country. In Vietnam, our PCV2 product was registered as a functional feed additive rather than as a pharmaceutical, enabling rapid market entry. Companion animal vaccines follow pharmaceutical regulatory frameworks, but typically with shorter timelines than human vaccines. These differences allow us to pursue a staged development strategy—starting with faster, more accessible applications, generating real-world validation, and gradually advancing toward more tightly regulated markets.

David Brühlmann [00:10:18]:
Okay, so it’s country-dependent. And as I recall, there are also major differences between human health and animal health regulations?

Masafumi Osawa [00:10:27]:
Yes. However, for companion animals, regulatory standards are often harmonized through VICH (International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products). For products like our PCV2 immune-enhancing feed additive, since there is no comparable product globally, the regulatory classification depends on how local authorities decide to position it.

David Brühlmann [00:10:55]:
Let’s look ahead. You’re still a relatively young company. What does the future hold? If we look at therapeutic areas, product types, or services, what are your next steps?

Masafumi Osawa [00:11:10]:
While vaccines represent our core focus, the silkworm system has broader therapeutic potential. Many antibodies and complex recombinant proteins are difficult to express in standard systems due to folding challenges or instability. Silkworm pupae, with their diverse cell types and chaperone-rich environment, offer an alternative solution for these difficult targets. Sustainability is another strong feature of silkworm biomanufacturing. Because the system requires minimal water, no bioreactors, and low energy inputs, the overall environmental footprint is significantly lower than conventional platforms. This opens possibilities for distributed manufacturing models where production can occur closer to the end user, including in emerging regions with limited infrastructure. In the long term, the flexibility of small-batch production means that silkworms may contribute to personalized biologics or rare disease therapeutics.

David Brühlmann [00:12:16]:
When do you think we’ll see the first biologic approved that was produced in silkworms? Do you have a sense of timing—five years, ten years?

Masafumi Osawa [00:12:27]:
That’s very difficult to answer because we are about to enter a Phase I clinical study next year—next summer, to be precise. I don’t know how many more years it will take, but it’s becoming very real. In the past, no one believed that a live silkworm body could be a source of APIs or vaccine antigens, but now it’s becoming a reality. Entering a Phase I clinical study means that products derived directly from silkworms are about to be administered to humans. So I cannot give a timeline, but this is a major step.

David Brühlmann [00:13:10]:
That’s a major milestone and shows that you’ve done the homework and achieved initial regulatory acceptance. Obviously, there’s still a lot ahead, but entering Phase I trials shows that regulatory bodies see the potential and trust the technology.

Masafumi Osawa [00:13:32]:
Yes. Regulatory authorities now accept our quality control strategy and how we manage consistency and safety, which opens the door to further pharmaceutical development opportunities.

David Brühlmann [00:13:45]:
Absolutely. You’ve demonstrated proof of concept, and once that foundation is laid, you can build on it. That’s wonderful. Before we wrap up, Masa, is there any burning question I haven’t asked that you’d like to share with our biotech community?

Masafumi Osawa [00:14:04]:
One thing I may not have mentioned is the production volume of a single silkworm pupa. Productivity is another strong advantage. One silkworm pupa, about 2 to 3 centimeters in size, can express 10 to 20 milligrams of norovirus virus-like particles (VLPs). After purification, this typically yields 1 to 2 milligrams per pupa, which is still a substantial amount. This is why scaling out is such a strong advantage of our platform. If we need 100 milligrams of product, we simply require 100 silkworm pupae. The total space needed is about the size of a laptop. Compared to large-scale manufacturing equipment, this is extremely compact, making it a key benefit of our platform.

David Brühlmann [00:15:09]:
As we wrap up, Masa, what is the most important takeaway from our conversation?

Masafumi Osawa [00:15:15]:
Silkworms were once used purely for silk production, and their pupae were often considered waste. Today, those same pupae have the potential to address major global health challenges and offer new modalities for vaccines and therapeutic proteins. If any researchers listening are struggling with difficult protein expression—whether VLPs, membrane proteins, or complex antigens—I would be very happy to explore how we can support your R&D.

David Brühlmann [00:15:49]:
This has been great, Masa. Thank you for sharing your work and for helping democratize life-saving therapies by pushing boundaries beyond what many people think is possible. Where can people connect with you?

Masafumi Osawa [00:16:08]:
Please feel free to connect with me on LinkedIn: Masafumi Osawa.

David Brühlmann [00:16:17]:
There you have it, Smart Biotech Scientists. Please reach out to Masa and learn more about the technology. Once again, thank you very much for being on the show today.

Masafumi Osawa [00:16:28]:
Thank you very much for having me, David. It was my pleasure.

David Brühlmann [00:16:33]:
Thank you for joining us for this deep dive into silkworm-based biomanufacturing with Masafumi Osawa. From ancient silk production to modern vaccine development, KAICO is proving that nature still has lessons to teach us about efficient bioprocessing. If this episode expanded your thinking about alternative expression platforms, please leave a review on Apple Podcasts or your favorite platform. Your feedback helps us bring you more cutting-edge biotech insights. Thank you so much for tuning in today and I'll see you next time.

All right, smart scientists, that's all for today on the Smart Biotech Scientist Podcast. Thank you for tuning in and joining us on your journey to bioprocess mastery. If you enjoyed this episode, please leave a review on Apple Podcasts or your favorite podcast platform. By doing so, we can empower more scientists like you. For additional bioprocessing tips, Visit us at www.bruehlmann-consulting.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let's continue to smarten up biotech.

Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.

Next Step

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About Masafumi Osawa

Masafumi Osawa brings more than a decade of experience in the pharmaceutical sector, with a strong focus on driving innovation to address global health needs. He is the Business Development Lead at KAICO Ltd., a Japan-based biotechnology start-up specializing in recombinant protein production using silkworms as biological reactors.

At KAICO, he leads strategic partnership development, represents the company at industry events and technical forums, and applies his strengths in market analysis, CRM, and communications to clearly articulate KAICO’s vision and promote its distinctive technologies, including oral vaccine platforms for both human and veterinary use.

Connect with Masafumi Osawa on LinkedIn.

He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.  

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