Friday, May 7, 2021

SARS-CoV-2 Spike Protein and Antibody Enhancement Effect - Open Questions Remain Unanswered

The latest data from Israel, which is a leader in vaccination, shows that fully vaccinated health care workers were less likely to develop SARS-CoV-2 in general, but that fully vaccinated individuals were statistically more likely to have the South African variant, as compared to unvaccinated controls.

Here are the studies I am referring to. The first study results:

Angel Y, Spitzer A, Henig O, et al. Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers. JAMA. Published online May 06, 2021. doi:10.1001/jama.2021.7152

Exposures Vaccination with the BNT162b2 vaccine vs unvaccinated status was ascertained from the employee health database. Full vaccination was defined as more than 7 days after receipt of the second vaccine dose.

Main Outcomes and Measures The primary outcome was the regression-adjusted IRR for symptomatic and asymptomatic SARS-CoV-2 infection of fully vaccinated vs unvaccinated health care workers. The secondary outcomes included IRRs for partially vaccinated health care workers (days 7-28 after first dose) and for those considered as late fully vaccinated (>21 days after second dose).

Results A total of 6710 health care workers (mean [SD] age, 44.3 [12.5] years; 4465 [66.5%] women) were followed up for a median period of 63 days; 5953 health care workers (88.7%) received at least 1 dose of the BNT162b2 vaccine, 5517 (82.2%) received 2 doses, and 757 (11.3%) were not vaccinated. Vaccination was associated with older age compared with those who were not vaccinated (mean age, 44.8 vs 40.7 years, respectively) and male sex (31.4% vs 17.7%).

Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated health care workers and 38 unvaccinated health care workers (incidence rate, 4.7 vs 149.8 per 100 000 person-days, respectively, adjusted IRR, 0.03 [95% CI, 0.01-0.06]).

Asymptomatic SARS-CoV-2 infection occurred in 19 fully vaccinated health care workers and 17 unvaccinated health care workers (incidence rate, 11.3 vs 67.0 per 100 000 person-days, respectively, adjusted IRR, 0.14 [95% CI, 0.07-0.31]). The results were qualitatively unchanged by the propensity score sensitivity analysis.

The second study results - Note this is a preprint and the comments section indicates that the implications of findings are in dispute:

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals.

Talia Kustin, Noam Harel, Uriah Finkel, Shay Perchik, Sheri Harari, Maayan Tahor, Itamar Caspi, Rachel Levy, Michael Leschinsky, Shifra Ken Dror, Galit Bergerzon, Hala Gadban, Faten Gadban, Eti Eliassian, Orit Shimron, Loulou Saleh, Haim Ben-Zvi, Doron Amichay, Anat Ben-Dor, Dana Sagas, Merav Strauss, Yonat Shemer Avni, Amit Huppert, Eldad Kepten, Ran D. Balicer, Doron Nezer, Shay Ben-Shachar, View ORCID ProfileAdi Stern doi:
…Here we tested the hypothesis that the B.1.1.7 and B.1.351 strains are able to overcome BNT162b2 mRNA vaccine protection. To this end, we identified individuals with documented SARS-CoV-2 infection – symptomatic or asymptomatic (hereby denoted as carriers) amongst members of the Clalit Health Services (CHS), the largest health care organization in Israel, which insures 4.7 million patients (53% of the population)...

...Vaccinated divided into two categories: (a) individuals who had a positive PCR test that was performed between 14 days after the 1st dose and a week after the 2nd dose (denoted as partial effectiveness, PE), and (b) individuals who had a positive PCR test that was performed at least one week after the second vaccine dose (denoted as full effectiveness, FE).

 ... a significantly higher proportion of B.1.351 was observed in FE cases vs. unvaccinated controls (OR of 8:1, one-sided exact McNemar test, p=0.02).

On the other hand, a significantly higher rate of B.1.1.7 was observed in PE cases vs. unvaccinated controls (OR of 26:10, one-sided exact McNemar test, p=0.006).

For B.1.351 in the PE category, the sparsity of data (one infection in each category) precluded statistical analysis (Fig. 2). 

A conditional logistic regression was further performed on the PE B.1.1.7 data (since more data was available in this category), supporting the previous analysis: an OR of 2.4 was observed (95% confidence interval of 1.2 to 5.1). Age was included in the regression and was found to be a non-significant confounder, suggesting that its possible role in propensity for infection by a specific strain was corrected through our matching scheme.

Early whistle-blowers indicated that there was a risk of antibody enhancement effect from both prior exposure to SARS-CoV-2 and vaccination aimed at eliciting the spike protein based on research from 2012 that found this effect in laboratory animals vaccinated with 5 vaccine candidates.

Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, Peters CJ, Couch RB. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012;7(4):e35421. doi: 10.1371/journal.pone.0035421. Epub 2012 Apr 20. Erratum in: PLoS One. 2012;7(8). doi:10.1371/annotation/2965cfae-b77d-4014-8b7b-236e01a35492. PMID: 22536382; PMCID: PMC3335060 

A critical outstanding question is this: Does the spike protein produced in vaccination result in an antibody enhancement effect when a vaccinated individual is exposed to a variant with immune escape properties. 

This is an empirical question. I have no bias. I want the vaccines to work but am concerned about the Salk Institute findings that the spike protein alone can affect vascular damage.

Lei et al. (2021, March 31). SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circulation Research, 128:1323–1326

I'll be following the data closely. I expect we will know the answer by December, 2021 when the South African, Indian, and Brazilian variants (among others with multiple hazardous mutations) grow in frequency.



  1. Yes this death on re-challenge has been known since the beginning of the COVID event. They killed every ferret and 20% of the Monkeys. Mice did better, somehow.

  2. There was information and statistics on the 2012 SARS vaccine enhancement before SARS-Covid19 hit, but information in difficult to find now. Every single vaccinated ferret, mouse, and non-human primate exposed later to SARS died.


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