Parasites, Antibody Dependent Enhancement (ADE) and Original Antigenic Sin (OAS)

A thought for someone else to run down

Early in the Covid catastrophe I became reacquainted with antibody dependent enhancement (ADE) and Original antigenic sin (OAS). They are two interesting quirks of the immune response, mainly to viruses and vaccines. Thinking about them, particularly OAS (which is a tendency for the immune system to imprint upon the first form of an antigen, making it somewhat difficult to zero in on iterations via subsequent exposure) I’ve wondered if part of what is at play here is our evolutionary history was likely much heavier with parasites, much lighter in viruses, and completely absent vaccines. Parasites are generally successful by evading the immune system in various ways…anyway, it just got me thinking. I posed the question to a few different AI platforms on Perplexity. There might be somethign to this line of thinking, perhaps not, but I wanted to share nonetheless.

Perplexity answer:

The hypothesis that antibody-dependent enhancement (ADE) and original antigenic sin (OAS) could be consequences of humans' historical high parasite burden is intriguing, but there's no direct evidence to support this claim. However, several aspects of parasite-host interactions and immune system evolution suggest potential connections:

Parasite-Induced Immune Modulation

Parasitic infections, particularly helminths, have significantly shaped human immune responses over evolutionary time8. Parasites have evolved mechanisms to evade and manipulate host immunity, often promoting a Th2-biased immune response9. This evolutionary relationship has led to the development of regulatory mechanisms in the human immune system to maintain a balance between parasite control and excessive inflammation8.

Potential Links to ADE and OAS

1. Th1/Th2 Balance: Parasites often induce a Th2-biased response, which could potentially influence antibody production and specificity9. This altered immune state might contribute to the conditions that allow ADE or OAS to occur in certain viral infections.

2. Immune Regulation: The immune-modulatory effects of parasites, including the induction of regulatory T cells and anti-inflammatory cytokines like IL-10, could potentially impact the quality and specificity of antibody responses79.

3. Cross-reactivity: Chronic exposure to diverse parasitic antigens might have shaped the human antibody repertoire, potentially increasing the likelihood of cross-reactive antibodies that could contribute to ADE or OAS in other infections23.

Evolutionary Considerations

The "Old Friends" hypothesis, an extension of the hygiene hypothesis, suggests that the human immune system evolved in the presence of certain microorganisms, including parasites8. The recent removal of these "old friends" in developed countries might contribute to immune dysregulation.

Limitations and Considerations

While these connections are theoretically plausible, it's important to note that:

1. ADE and OAS are primarily observed in viral infections, not parasitic ones12.

2. The mechanisms of ADE and OAS are complex and likely involve multiple factors beyond just parasite exposure36.

3. Direct evidence linking historical parasite burden to these phenomena is currently lacking.

In conclusion, while the historical prevalence of parasitic infections has undoubtedly shaped human immune responses, more research is needed to establish any direct causal relationship between this evolutionary history and the occurrence of ADE or OAS in modern viral infections.