More Evidence that Innate Neutralizing Antibodies to HERV-K102 Envelope Contribute to COVID-19 Protection and "In Vitro Neutralizing Titres" in HUMANS Depending on the Methods Used
HERV-K102 is Unique to HUMANS
Figure 1. Because SARS-CoV-2 is an enveloped RNA virus (buds from the cell surface as opposed to lytic release), HERV-K102 envelope which becomes expressed at the cell surface of SARS-CoV-2 infected HUMAN cells becomes associated with SARS-CoV-2 virions. This enables the INNATE antibodies to HERV-K102 envelope to clear and neutralize SARS-CoV-2 virions. So any in vitro neutralization test that uses human cells for propagation of the live virus or the pseudotyped virus, will reveal neutralization by spike specific antibodies or HERV-K102 envelope specific antibodies.
In a commentary on antigenic imprinting last May, Reincke SM et al. [1], wrote that a third dose of the mRNA vaccines (using the ancestral sequences) restored neutralization titres against Omicron comparable to that against Delta after two doses [2] but which, interestingly, was not observed in monkeys [3].
From their Figure 2 [2] as shown here in Figure 2, we can see that this enhancement of neutralization was only detected when the virus used for the neutralization test was in fact cultured in human cells (ie., the pseudovirus used in Figure 2a from human HEK293T/17 cells) but not when live/intact SARS-CoV-2 was isolated from green monkey Vero 76 cells (ie.,. live virus grown on green monkey cells).
Figure 2. Evidence that Producing Pseudotyped Virus in HUMAN Cells Detects Innate Neutralizing Antibodies (Like Those that recognize HERV-K102 Envelope)
This tells us that using pseudotyped viruses grown in human cells will complicate the interpretation of “antigenic imprinting” research and will obscure the source of observed in vivo protection against SARS-CoV-2.
All cases of claims that spike specific neutralizing IgG protects against SARS-CoV-2 involved the use of pseudoviruses and/or used human cells for detection (the latter which might artificially reveal the protector activity of HERV-K102 particles in plasma).
All neutralization research performed with SARS-CoV-2 pseudoviruses produced in human cells and/or when human cells are used as indicator cells in neutralization assays, must be taken with a grain of salt.
References
1. Reincke SM, Prüss H, Wilson IA, Kreye J. Antigenic imprinting in SARS-CoV-2. Clin Transl Med. 2022 Jul;12(7):e923. doi: 10.1002/ctm2.923.
2. Quandt J, Muik A, Salisch N, et al. Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation. bioRxiv. 2022. https://doi.org/10.1101/2022.04.01. 486695.
3. Gagne M, Moliva JI, Foulds KE, et al. mRNA-1273 or mRNA Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron. Cell. 2022;185:1556-1571.
Doesnt that also tell us that doing in vitro studies with non-human cells has limited utility wrt helping humans? I guess this study didnt look at "humanized" mice cells though. Should we accept antibody titre results from 8 mice to "approve" vaccines (nevermind the complete lack of safety data)?