Omicron infections elicit neutralizing antibodies against other variants of concern

Update July 14, 2022: The featured study in this article is now published in Clinical and Translational Medicine.

A preprint study from Hong Kong University shows that an Omicron infection elicits an immune response against several SARS-CoV-2 variants of concern.

As a snapshot, the study involved two previously vaccinated people who had an omicron infection. Their antibody titers were initially low. After a few days, their neutralizing antibodies against the SARS-CoV-2 with the D614G mutation and five variants ( Alpha, Beta, Gamma, Pi, and Delta) went up. Not only that, the CD4+ and CD8 T-cells also increased!

The paper is Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses and was released two days ago at bioRxiv. [1]

The Study subjects

Omicron patient one (OP1) is a 62-year-old male who is fully vaccinated. He started having COVID symptoms 178 days (6 months) after getting the Pfizer (BNT162b2).

Omicron patient two (OP2) is a 37-year-old male who started having symptoms 54 days after complete vaccination with Moderna.

Both cases had mild symptoms but were hospitalized (for isolation and observation). They did not require oxygen supplementation or ICU care.

Thirty-four vaccinees who are not infected with Omicron were also included for comparison. All were fully vaccinated with Pfizer, and serum was taken from them 30 days after the second shot when the antibody levels were at their peak.

The table below shows the two omicron patients and the control group.

Antibody results

Baseline antibodies levels from the uninfected

To determine how effective the antibodies from previous Pfizer shots are, they compared the antibody response of the 34 vaccinees who were not infected with Omicron to the wild type (WT) and five other variants. The wild type is the SARS-CoV-2 with the first significant mutation (D614G) that increased its infectivity.

The variants of concern are Alpha, Beta, Gamma, Delta, and Omicron.

Previous research has shown that antibodies against the SARS-CoV-2 can be detected in the serum within 1-3 weeks after infection[2],[3].

Back to the study, you can see from the table below that the antibodies from the 34 vaccinees can neutralize the Alpha and Gamma variants, but there is no neutralization among the Beta, Delta, and Omicron variants. Neutralizing antibodies block the attachment of the spike protein to ACE2 receptors and prevent infection.

The Omicron has the most significant resistance to neutralizing antibodies compared to D614G (-5.90) and explains why it is highly contagious.

Breakthrough neutralizing Antibody response of oP1 and OP2

Surprisingly, the neutralizing antibody levels against all variants, as indicated by the different colors below, went up significantly after a few days!

Initially, the antibodies of omicron patient 1(OP1, Pfizer) were unmeasurable at <1:20 IC50 values, and then it went up to 1:2,929 at nine days. IC50 measures the amount of neutralzing antibodies in this study.

For OP2 (Moderna), the neutralizing antibodies rose from a mean IC50 of 1:24.3 to 1:854.5 at 12 days in OP2 post symptoms onset (PSO)

Antibodies after breakthrough infections are higher than antibodies from the 34 vaccinees.

The graphs below show the rise of the neutralizing antibodies of OP1 and OP2 against all the variants of concern. The increase of antibodies against the Beta is 121.41 fold higher, and for Omicron, the rise is 74.89 times higher than the Pfizer vaccinees that were not infected.

Not included in the graph is the increase in the neutralizing antibodies of OP1 against 15/16 variants with individual mutations or deletions that make them resistant to vaccine-induced neutralizing antibodies. The authors conclude,

These results demonstrated that, although the Omicron variant of concern evaded BNT162b2-vaccine-induced neutralizing antibodies, the breakthrough infection (caused by Omicron) elicited cross-reactive breakthrough neutralizing antibodies generally against all current variants of concern in both OP1 and OP2.

But there’s more.

B cells producing anti-spike antibodies increased.

There is more to the immune response than antibodies. The authors also measured the B cells in OP1 and OP2. B cells produce antibodies (immune globulins, IgG) specific to the spike protein of the SARS-CoV-2. We call them spike-specific IgG+ B cells.

The bar graphs below show the high levels of the B-cells in OP1 (13.2%) than OP2 (2.31%). The vaccinees only had an average of 1.12% increase at their peak responses.

CD4 and CD8 T-cells also increased

Interferon-gamma is a critical cytokine for innate and adaptive immunity against viral infections. They are produced by CD4 (T-helper cells) and CD8 (cytotoxic) T lymphocytes.

There is more increase in OP1 who had Pfizer than OP2 and the uninfected vaccinees.

What about the unvaccinated? The unvaccinated are not included in the study. However, one research showed that People who recovered from COVID-19 have effective T-cells against the Omicron. So it is highly probable that neutralizing antibodies against several variants could also rise too, but that remains to be documented.

In summary, the study shows that an omicron infection can elicit neutralizing antibodies and T-cells against several SARS-CoV-2 variants of concern.

The authors make the recommendation that an Omicron-based vaccine should be made. I beg to disagree. Since many studies have shown that the omicron variant causes mild disease, why not allow people to get infected but give them early treatment?

An Omicron infection is like vaccination

Dr. Robert Malone said that the Omicron variant behaves like a live-attenuated vaccine that can elicit a robust immune response. I quoted him at Multinational study shows why the Omicron variant has low fatality and high infectivity.

Quarantines have psychological, health, and economic repercussions not to mention that the COVID shots have many adverse effects like myocarditis.

Blood clots

And deaths.

Don’t Get Sick!

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References:

Zhou et al. Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses. bioRxiv 2021.12.27.474218; doi: https://doi.org/10.1101/2021.12.27.474218
Qu J et al. Profile of immunoglobulin G and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Nov 19;71(16):2255-8.
Wolfel R, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 May;581(7809):465-9.

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