What could go wrong with an HIV vaccine?

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 From Perplexity

What bad things could happen if an mRNA vaccine is created for an exogenous retrovirus that turns out to be an endogenous retrovirus?

If an mRNA vaccine is designed to target what is thought to be an exogenous retrovirus (a virus that infects the body from the outside) but it actually targets an endogenous retrovirus (a viral sequence that is already integrated into the human genome), several significant risks could emerge:

1. Autoimmune Reactions

  • mRNA vaccines prompt the body to make a viral protein; the immune system learns to attack cells displaying that protein.

  • Endogenous retroviruses (ERVs) are embedded in every human cell's DNA. If the vaccine-trained immune system begins targeting proteins from ERVs, it could:

    • Attack normal cells expressing these proteins.

    • Cause chronic inflammation, tissue destruction, and potentially trigger or worsen autoimmune diseases (such as lupus or multiple sclerosis).

2. Off-target and Broad Immune Responses

  • ERVs are diverse and some have regulatory roles in embryonic development, immune function, and placental biology.

  • An immune response against ERV proteins could unintentionally damage tissues where these sequences are active, such as the placenta during pregnancy or regenerative tissues.

3. Chronic Inflammation and Tissue Damage

  • Unlike exogenous viruses, ERVs are present throughout the body and expressed at low levels in many tissues.

  • Persistent antibody or T-cell response against ERV proteins may lead to chronic inflammation and long-term tissue damage in multiple organs.

4. Molecular Mimicry and Cross-Reactivity

  • If the targeted ERV proteins are structurally similar to other human proteins, this might lead to cross-reactivity, where the immune system starts attacking unrelated but similar-looking proteins in the body, causing further autoimmunity.

5. Risk of Developmental Abnormalities

  • Some ERVs are critical for normal development. For example, syncytins (derived from ERVs) play a crucial role in placental formation.

  • An immune attack against such proteins, especially in pregnant women, could impair pregnancy outcomes or fetal development.

Key Takeaway

Targeting endogenous retroviral proteins with a vaccine risks training the immune system to attack normal, healthy bodily cells and tissues, with the potential for severe, widespread autoimmune and inflammatory consequences.

“Because ERVs are present in the genome and expressed in some tissues, a vaccine targeting their proteins could cause the immune system to attack self tissues, potentially leading to autoimmunity or damaging key biological processes.”

References

: “Vaccination against endogenous retroviruses: therapeutic potential and risks,” Nature Reviews Immunology (summary)
: “Endogenous retroviruses: with us and against us,” Frontiers in Immunology (overview)
: “Expression and functions of human endogenous retrovirus genes: Disease associations and biological roles,” Cellular & Molecular Immunology (review)

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