Recombinant Spike Protein Using Insect Cells in Nuvaxovid Vaccines Carry Strange Sugars That Can Trigger Unexpected Immune Reactions!
Nikhil Prasad Fact checked by:Thailand Medical News Team May 12, 2025 6 hours, 38 minutes ago
Medical News: A groundbreaking new study by researchers from the University of Natural Resources and Life Sciences in Vienna (Universität für Bodenkultur), the University of Veterinary Medicine Vienna, Maynooth University in Ireland, and the University of Southampton in the UK has uncovered unusual and potentially concerning sugar molecules, or “glycans,” on the surface of spike proteins used in certain COVID-19 vaccines like Nuvaxovid, which are made using insect cell technology.
Recombinant Spike Protein Using Insect Cells in Nuvaxovid Vaccines Carry Strange Sugars That Can Trigger Unexpected Immune Reactions!
The researchers focused on glycoproteins—proteins decorated with sugar chains—produced using insect cell lines derived from two moth species: Spodoptera frugiperda (Sf9 cells) and Trichoplusia ni (High Five cells). These insect cells are widely used in vaccine manufacturing, including for Novavax’s COVID-19 vaccine, Nuvaxovid. This
Medical News report highlights that while this technology offers advantages in speed and cost, it may come with hidden immunological risks.
Why Sugar Coatings on Proteins Matter
Glycans, or sugar structures, are not just decorative—these microscopic sugar molecules help proteins fold correctly and influence how our immune system recognizes foreign particles. In humans, glycans follow a particular pattern. However, insect cells, as used in the Novavax vaccine and others like the influenza vaccine Flublok, produce glycoproteins with very different sugar modifications.
What the researchers found was shocking. The spike proteins made in insect cells had complex sugars never seen before in human biology—some of which can interact with our immune system in unpredictable ways.
The Strange Sugars Found
Using high-tech mass spectrometry and advanced protein modeling, the research team discovered a set of unusual modifications on glycoproteins derived from insect cells. These include:
-Zwitterionic glycans: Sugars that carry both positive and negative electrical charges. These are extremely rare in human biology.
-Phosphorylcholine-modified glycans: Sugars that carry phosphorylcholine, a molecule known to trigger strong immune responses. These modifications were found to bind to human C-reactive protein (CRP), a key component of the innate immune system.
-Core difucosylation: A sugar pattern where two fucose molecules are added, which is uncommon in humans and can act as an allergen in some people.
-Glucuronic acid and pentose additions: These were found especially in Sf9 cells and included glycan structures never previously reported, containing sugar units like xylose and glucuronic acid arranged in highly unusual patterns.
Interestingly, the e
xact glycan structures varied depending on which insect cell line was used. High Five cells had more core difucosylation, while Sf9 cells had more zwitterionic sugars and other exotic structures.
How This Affects Vaccines Like Nuvaxovid
The Novavax COVID-19 vaccine, known as Nuvaxovid, uses a spike protein manufactured in Sf9 insect cells. The study revealed that this spike protein carried multiple unusual sugar modifications. Most significantly, traces of phosphorylcholine and difucosylated sugars were detected, alongside traditional oligomannose structures. Some glycans even carried sulphate groups—another modification that can activate the immune system.
These findings are important because the sugar decorations on viral spike proteins can influence how our immune system reacts to the vaccine. If the sugars are too foreign, the immune system may not just attack the virus but also react to the sugars themselves, potentially leading to unwanted inflammation or immune complications.
The Implications for Safety and Immune Reactions
While recombinant vaccines like Nuvaxovid are claimed to be safe and effective, this study raises questions about how overlooked sugar structures might affect certain people. Phosphorylcholine, for example, can modulate immune responses and even interfere with complement proteins that form a first line of defense in our body. Moreover, sugar patterns like difucosylation are known allergens in people with sensitivities to insect venom or parasitic infections.
The authors caution that these strange sugars could potentially:
-Trigger allergic or autoimmune reactions in susceptible individuals
-Alter the expected immune response to the vaccine
-Interact with components of the innate immune system like CRP and mannose-binding lectins
-Lead to antibody responses not only against the spike protein but against the sugars themselves
How the Study Was Conducted
The scientists used advanced glycoproteomic techniques to study both the natural glycoproteins inside insect cells and those engineered for vaccine use. They analyzed spike proteins from Novavax’s Nuvaxovid vaccine, as well as various influenza hemagglutinins produced using the same technology.
By breaking down the glycoproteins into smaller pieces and examining them under high-resolution mass spectrometers, they could identify not only the peptide sequences but also the exact sugar structures attached. They also used molecular modeling to understand how the location of sugar sites on proteins might affect accessibility for enzymes that build or trim these sugar chains.
A Closer Look at the Spike Protein
In total, the SARS-CoV-2 spike protein used in Nuvaxovid has 22 potential sites for N-glycosylation—places where sugars can attach. The researchers found that:
-Most sites carried simple sugars like mannose
-Some sites were modified with complex sugar chains including phosphorylcholine and core fucose
-A few rare sites even carried sulphated sugars, which can influence inflammation
-The diversity of glycans depended not only on the protein sequence but also on which part of the cell machinery could access the glycosylation site, which the team confirmed using detailed molecular simulations.
Why This Matters More Than Ever
As biotechnology companies turn more frequently to insect cell systems to produce therapeutic proteins and vaccines, this study is a reminder that even the smallest details—like the sugars attached to proteins—can have major consequences.
These unusual glycan patterns are often overlooked in quality control, as current methods focus more on protein structure than sugar analysis. The researchers emphasize that greater attention needs to be paid to glycosylation when producing vaccines in non-human systems.
Conclusion
The study provides compelling evidence that recombinant spike proteins used in insect-cell-derived vaccines like Nuvaxovid carry a mix of unusual and potentially immunogenic sugar structures. These include zwitterionic, phosphorylcholine-modified, sulphated, and core difucosylated glycans that are rarely found in the human body and can interact with our immune system in unexpected ways. Although the presence of these sugars does not automatically mean the vaccines are unsafe, it raises critical questions about long-term immune responses and the possibility of side effects in sensitive individuals.
The researchers recommend that all glycosylation profiles of proteins produced in insect cells be carefully analyzed using updated analytical tools that can detect these exotic sugars. Only by fully understanding these subtle differences can we ensure the safest and most effective use of recombinant vaccines and therapeutics.
The study findings were published in the peer reviewed journal: Molecular & Cellular Proteomics.
https://www.mcponline.org/article/S1535-9476(25)00079-9/fulltext
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