What Is the Difference Between Recombinant and Native Antigens

What Is the Difference Between Recombinant and Native Antigens

Antigens are crucial for understanding how our immune system fights off diseases. These substances, which can be anything from a virus to a piece of pollen, trigger an immune response in our bodies.

There are two main types: native antigens that come directly from the source like bacteria or viruses, and recombinant antigens made through genetic engineering. While native antigens offer a closer look at real-life infections, recombinant antigens provide a safer and more consistent way to produce large quantities without the presence of the actual disease-causing pathogen.

Each diagnostic application has unique requirements and for this reason assay developers may have different preferences when using recombinant or native antigens.

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Recombinant vs Native Antigens: Key Differences & Characteristics

Differences between recombinant and native antigens can be found in their sources, production methods, stability, shelf life, and usage in immunoassays. Native antigens offer assay developers authenticity but are complex and costly to isolate. On the other hand, recombinant antigens allow for streamlined manufacturability and scalability as well as lot-to-lot consistency, a key factor in developing consistent and reliable diagnostics.

Understanding these distinctions helps assay developers make informed decisions about which type of antigen will best meet their needs for test sensitivity, consistency, shelf life and more.

Types of Antigens (Native and Recombinant)

Antigens are crucial in the study and diagnosis of various diseases. They come in two main types: native and recombinant. Each serves an important role in diagnostics with distinct characteristics that make them suitable for different applications.

  1. Native antigens are those derived directly from their natural source. These antigens are isolated from the actual virus, bacteria, or other pathogens they originate from. For assay developers focusing on autoimmune disease antigens or infectious disease antigens, using native antigens means working with materials that closely mimic what the immune system encounters. This similarity can lead to high sensitivity in diagnostic tests.
  2. Recombinant antigens, on the other hand, are produced through genetic engineering. Scientists insert DNA that codes for the target antigen into bacteria (e.g., E coli/prokaryotic cells) or viruses (e.g., baculovirus via insect cells/eukaryotic cells) , which then produce it in large amounts. This method allows for the consistent production of antigens without needing access to the original pathogen—a significant advantage when dealing with dangerous or hard-to-find viruses and bacteria.

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Key Differences Explained: 

There are four unique characteristics to observe and understand when looking at the key differences between native and recombinant antigens.

  1. Source: Native antigens derive directly from their original biological context; recombinant antigens are generated artificially using DNA technology.
  1. Production: Isolating native antigens often involves complex extraction processes from infected tissues or cultured cells. Producing recombinant antigens involves an advanced procedure that requires genetic engineering but offers scalability.
  2. Stability and Shelf Life: Since recombinant antigens may be engineered to exclude the destabilizing sequences found in naturally occurring proteins, they frequently exhibit higher stability and longer shelf lives than their native counterparts.
  3. Use in Immunoassays: Native antigens excel in tests requiring high fidelity to natural infection conditions due to their comprehensive representation of epitopes—the parts of an antigen molecule to which an antibody attaches itself. Meanwhile, recombinant antigens offer consistency and specificity, reducing background noise caused by non-target reactions.

Whether the assay requires native or recombinant antigens, consistency, quality, and performance are key factors when sourcing these reagents. Surmodics IVD is the proud North American representative for DIARECT™ Antigens and Antibodies, now part of BBI™ Solutions. DIARECT recombinant and native antigens have a proven track record for quality and sensitivity in ELISA, Western Blot, and lateral flow applications. The lot-to-lot consistency of DIARECT antigens and antibodies reduces development time and increases productivity of immunoassay developers.

All of the DIARECT antigens and antibodies are produced under an ISO 13485:2016 Certified Quality System.

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Understanding the differences between recombinant and native antigens starts with considering their sources. The origin of these antigens is pivotal, as it influences everything from their production process to their use in various applications, especially in the development of immunoassays.

Aspect Native Antigens Recombinant Antigens


Antigens isolated directly from the pathogen or cells under natural conditions. Antigens produced through genetic engineering, where genes encoding the antigen are inserted into expression systems.

Source Material

Pathogens, infected tissues, or cells.

Plasmids or vectors in bacteria, yeast, or mammalian cells.

Extraction Process

Involves purification from the pathogen or infected tissue, which can be complex and time-consuming. Employs biotechnological methods to grow host cells that express the target antigen, followed by purification.


Reflects the natural composition and post-translational modifications. Allows for specific mutations or tags to aid in purification and detection; may lack some post-translational modifications.

Exploring the source of these antigens unveils a fundamental distinction—native antigens come directly from their natural environment, embodying the true essence of the pathogen. In contrast, recombinant antigens are the product of cutting-edge genetic engineering, providing a customizable approach to antigen production. This foundational difference sets the stage for examining other facets, such as the production processes of both types of antigens.


Between native and recombinant antigens, significant distinctions arise, particularly in how they are produced. These disparities not only influence their availability and scalability but also their reliability in various applications.

Aspect Native Antigens Recombinant Antigens

Source Material

Natural tissues or cells

Genetically engineered cells


Isolation and purification from the original organism

Expression in a host system followed by purification


Limited by source availability

Highly scalable, as it depends on the host's growth


Varies with source material

More uniform, controlled by genetic sequences

Time and Cost

Often more time-consuming and costly due to complex extraction Generally, less time-consuming and cost-effective at scale

The production of antigens is a pivotal factor assay developers consider, as it impacts not just the cost and time but also the reliability and uniformity of the tests they develop. Whether choosing native or recombinant antigens, developers factor these aspects into their decision-making process, seeking to balance scientific needs with logistical realities. Each method has its own set of advantages and challenges, shaping the landscape of immunoassay test development.

Stability and Shelf Life

Understanding the stability and shelf life of native versus recombinant antigens is crucial for assay developers, as these factors significantly impact the practicality and efficiency of diagnostic tests.

Aspect Native Antigens Recombinant Antigens


Varies widely, often less stable due to complex structures and the presence of post-translational modifications. Generally, more stable due to simpler structures and the absence of post-translational modifications that affect stability.

Shelf Life

Shorter, due to sensitivity to environmental conditions such as temperature and pH. Longer, as they are less sensitive to environmental conditions and can be engineered for enhanced stability.

For assay developers, this comparison makes clear that while native antigens offer a closer mimicry to natural infection, their stability and shelf life might limit their use in some diagnostic applications. Recombinant antigens, on the other hand, present a more stable and durable option, facilitating broader application in immunodiagnostic tests. This balance between mimicking natural infections and ensuring test viability and reliability underscores the importance of selecting the appropriate antigen type for specific diagnostic needs.

Use in Immunoassays 

Recombinant antigens are extensively used in immunoassays due to their consistent production and purity, which ensures accurate and reliable results. Their defined composition makes them ideal for standardizing diagnostic assays, leading to increased precision.

Native antigens are also employed in immunoassays, particularly when the natural conformation is crucial for the assay's efficacy. They offer a more authentic representation of the pathogen but may present challenges regarding lot-to-lot consistency.

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Benefits and Challenges of Native and Recombinant Antigens

As previously mentioned, native antigens offer natural conformation and post-translational modifications, whereas recombinant antigens allow for controlled production and consistency in quality. The following section takes a deeper look at the key advantages of each unique antigen type and how their differences may impact an assay developers’ decision on which protein is optimal for their unique application.

Native Antigens

Native antigens are proteins derived from the organism of interest, providing a more natural representation of the pathogen. The isolation method needs to maintain the protein's structural and functional integrity to ensure effectiveness in immunoassays.

This approach may be preferable when targeting specific epitopes that might not be correctly folded in recombinant forms. Native antigens can offer a closer match to the actual infection, potentially leading to improved sensitivity and specificity in assays.

Recombinant Antigens

Recombinant antigens are lab derived. They are designed to mimic the structure of antigens found in viruses, bacteria, or other pathogens. One significant advantage is that they can be easily manufactured in large quantities, making them readily available for diagnostic tests and vaccines.

Their stable production process ensures consistent quality and purity, which is vital for accurate assay results. The use of recombinant antigens has revolutionized diagnostics through their standardized and reliable nature.

Which is the Right Choice?

In conclusion, the choice between native and recombinant antigens depends on specific assay requirements. Understanding their differences is crucial for making an informed decision.

For assay developers, the decision between native and recombinant antigens depends on their specific assay requirements. Native antigens offer a more authentic representation of the target molecule but may be limited in supply.

Recombinant antigens provide consistency and scalability, making them suitable for high-throughput assays. Understanding the unique needs of the assay will guide developers in selecting the most appropriate antigen type to ensure accurate and reliable results.

Considerations for choosing between native and recombinant antigens involve assessing assay demands such as specificity, reproducibility, and practicality in large-scale production.

Ultimately, aligning the choice with assay goals is pivotal for achieving optimal performance.

Considerations for Choosing Between Native and Recombinant Antigens

When it comes to choosing between native and recombinant antigens, assay developers should carefully evaluate the intended application and required characteristics. Native antigens are ideal for assays where conformational epitopes are crucial, while recombinant antigens offer consistent purity and lot-to-lot consistency.

Assay developers must meticulously analyze the biological relevance of their assays before selecting between native and recombinant antigens. It not only depends on specific requirements but also dives into seeking more than just an adaptable solution; it's about unlocking the secrets that best suit their needs within the ever-evolving world of immunodiagnostics.

Surmodics IVD is here to help address any questions you may have regarding our supply of gold standard antigens and antibodies from DIARECT. Choosing between native and recombinant antigens can be challenging, working with Surmodics IVD can help ease this decision process.

Contact our team today to learn more about Surmodics’ supply of DIARECT native and recombinant antigens!

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