There is an antibody-dependent enhancement (ADE) of SARS-CoV-1 infection. Notably, some vaccines enhance infection.

Fig. 2. Model of immunopathological events associated with SARS clinical evolution. SARS patients mount robust IFN-mediated innate immune responses during early (acute) illness and peak symptomology. Following the median SO2 nadir in surviving patients (late SARS), most SARS patients resolve inflammation and mount effective adaptive immunity against SARS CoV. Immune dysregulation in severe SARS patients is hallmarked by continued expression of inflammatory chemokines and ISGs and deficiencies in MHC and Ig gene expression. Immune-mediated pathology worsens in the minority of susceptible SARS patients and unresolved CXCL10 expression and viral burden is associated with poor outcome. Source: Cameron, 2007.

Last update and review: June 7, 2020.


Introduction.

Remotely controlled (by who?) idiotic bureaucrats around the world have already announced a plan to introduce compulsory vaccinations against SARS-CoV-2. According to the plan, people will not be able to return to work, to travel, and even to exit their homes, unless they are vaccinated.

Remotely controlled (by who?) idiotic bureaucrats around the world have already announced a plan to introduce compulsory vaccinations against SARS-CoV-2. The important question of who holds the Remote Control that activates the idiotic bureaucrats around the world is discussed elsewhere. The important piece of information discussed here and in other articles on this website is about safety concerns around coronavirus vaccines. Some vaccines against animal coronaviruses have been successfully generated, but their development has proven very difficult due to immune enhancement of disease in vaccinated recipients.

The important question of who holds the Remote Control that activates the idiotic bureaucrats around the world is discussed elsewhere in our articles and on social networks.

In this article, you can find several curated citations from Jaume et al., 2011 (1), that describe mechanisms of SARS-CoV-1 (2002-2004) infection and how antibody to SARS-CoV-1 can enhance infection instead of limiting it. SARS-CoV-1 and SARS-CoV-2 are very similar. There is an extensive body of literature on SARS-CoV-1 and it is highly relevant to the current COVID-19 epidemic.

Deregulation of host inflammatory/immune responses is a hallmark of both “SARS”.

It has been hypothesized that deregulation of host inflammatory/immune response is a hallmark of both “SARS” (stands for severe acute respiratory syndrome), the 2002-2004 SARS, and the current COVID-19 SARS. Jaume and colleagues, 2011 (1), investigated immune cells related pathogenesis of the SARS-CoV-1 virus.

Jaume and colleagues, 2011 (1), on antibody-dependent enhancement (ADE) of SARS-CoV-1 infection, including ADE after a vaccination.

Jaume et al., 2011 (1):

We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro.

Anti-Spike immune serum potentiated infection of immune cells by replication-competent SARS-CoV-1 coronavirus.

We demonstrate here that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus.  Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells despite their comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it.

Some vaccines against animal coronaviruses have been successfully generated, but their development has proven very difficult due to immune enhancement of disease in vaccinated recipients (28, 53, 65).

Several reports have highlighted the direct infection of hematopoietic cells by SARS-CoV (19, 39, 74); however, it is not yet clear how SARS-CoV gets a foothold into immune cells, which do not express the SARS-CoV receptor ACE2 (20, 21).

“Antibody-mediated infection of feline coronavirus not only enhances viral progeny but also dramatically increases production of tumor necrosis factor alpha by infected cells.”

Interestingly, antibody-mediated infection has been shown to elicit markedly distinct responses compared to viral entry through the natural host receptor (23, 45, 58, 62). Indeed, antibody-mediated infection of feline coronavirus not only enhances viral progeny but also dramatically increases production of tumor necrosis factor alpha by infected cells. The hyperinduction of the proinflammatory cytokine is believed to account for the exacerbated apoptosis of the neighboring leukocytes (61, 62).

Because it has been hypothesized that deregulation of host cytokine/chemokine responses is a hallmark of SARS (7, 27, 35, 43, 70), it would be interesting to investigate how ADE of SARS-CoV infection may contribute to the disease pathogenesis.

SARS-CoV-1 can enter into target cells that do not express the conventional virus receptor ACE2.

Altogether, our results report a novel mechanism by which SARS-CoV can enter into target cells that do not express the conventional virus receptor and are otherwise refractory to the virus. This may have implications for understanding the tropism and pathogenesis of the virus and highlight potential pitfalls associated with immunization against this coronavirus. These findings should prompt further investigations for a better understanding of the molecular and cellular mechanisms underlying ADE of SARS-CoV infection. The consequences of this alternative infection pathway on the functionality and/or homeostasis of the target cells also need to be resolved.

SARS-CoV vaccine against Spike-protein potentiated infection of human immune B cells with SARS-CoV. Yet, a majority of vaccines in development target the same Spike-protein of the virus.

Most of the SARS-CoV-2 potential vaccines target S protein (Spike protein of the virus). But as described above, there is an antibody-dependent enhancement (ADE) of the infection associated with vaccine candidates that target spike-protein of SARS-CoV-1. It is, therefore, possible that the population will be forced to get injected with a “vaccine” that actually enhances infection.

A majority of SARS-CoV-2 vaccines in development as of March 2020 target Spike protein. Yet, this type of vaccine enhances infection in previous vaccine candidates for SARS-CoV-1 and animal coronaviruses. Source of the table: Amanat and Krammer, 2020 (3).
A majority of SARS-CoV-2 vaccines in development as of March 2020 target Spike protein. Yet, this type of vaccine enhances infection in previous vaccine candidates for SARS-CoV-1 and animal coronaviruses. Source of the table: Amanat and Krammer, 2020 (3).

The timeline of immunological events suggests that antibody-dependent enhancement of the SARS-CoV-2 infection is possible.

It is of note that the timeline of immunological events observed during SARS 2002-2004 disease seems to be in accordance with the findings of Jaume et al., 2011 (1). Indeed, the adaptive immune system comes at full force between the 7th and 14th days from the onset of disease. If antibody-dependent enhancement occurs, it may be another factor contributing to the immune dysregulation observed in severe SARS (2002-2004).

Fig. 2. Model of immunopathological events associated with SARS clinical evolution. SARS patients mount robust IFN-mediated innate immune responses during early (acute) illness and peak symptomology. Following the median SO2 nadir in surviving patients (late SARS), most SARS patients resolve inflammation and mount effective adaptive immunity against SARS CoV. Immune dysregulation in severe SARS patients is hallmarked by continued expression of inflammatory chemokines and ISGs and deficiencies in MHC and Ig gene expression. Immune-mediated pathology worsens in the minority of susceptible SARS patients and unresolved CXCL10 expression and viral burden is associated with poor outcome. Source: Cameron, 2007.
Fig. 2. Model of immunopathological events associated with SARS clinical evolution. SARS patients mount robust IFN-mediated innate immune responses during early (acute) illness and peak symptomology. Following the median SO2 nadir in surviving patients (late SARS), most SARS patients resolve inflammation and mount effective adaptive immunity against SARS CoV. Immune dysregulation in severe SARS patients is hallmarked by continued expression of inflammatory chemokines and ISGs and deficiencies in MHC and Ig gene expression. Immune-mediated pathology worsens in the minority of susceptible SARS patients and unresolved CXCL10 expression and viral burden is associated with poor outcome. Source: Cameron, 2007.

Selected references:

1. Jaume M, Yip MS, Cheung CY, et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway. J Virol. 2011;85(20):10582–10597. doi:10.1128/JVI.00671-11

2. M.J. Cameron et al. / Virus Research 133 (2008) 13–19 17

3. Amanat and Krammer, SARS-CoV-2 Vaccines: Status Report, Immunity (2020), https://doi.org/10.1016/