A discussion of natural immunity and vaccines in light of recent COVID-19 mutant strains

We are now in a race between COVID-19 vaccine distribution and a virus that is rapidly mutating. Health-care workers have been prioritized to be among some of the first to receive the vaccine. New information is constantly coming to light, and the messages can often be inconsistent. Here, we will attempt to address a few of these pertinent issues. The contents in this article are in no way definitive, and further peer-reviewed studies are needed to validate many of these preliminary findings.

Antibody response to vaccines and natural immunity

Although there is conflicting data, studies have shown waning immunity in patients who have previously had COVID-19, especially those who have had asymptomatic or mild disease. In a study from of the University of California, Los Angeles (UCLA), patients with mild to moderate disease had IgG titers (long-term antibodies) measured one month out from infection and witnessed mean levels quickly begin to fade over the course of the next 90 days.¹ Data from multiple other studies also show a wide spectrum in antibody levels that often exhibit high correlation to disease severity.²

The data in regard to vaccine antibody production, however, has been much more consistent. Both vaccines with emergency use authorization (Pfizer and Moderna) are reporting results of neutralizing antibody geometric mean titers (GMTs) several times greater than mean levels in convalescent serum panels from patients with previous exposure to COVID-19.^3,4 The current assumption is that greater antibody production will confer greater immunity to the individual.

Vaccine response in patients with previous COVID-19 infection

A topic of debate has risen as to whether those patients who have previously contracted COVID-19 should get vaccinated. To shed further insight into this complex mosaic of interaction regarding immune response, vaccines, and COVID-19, many are looking at the data coming out of Israel. Israel is leading the world in vaccination rates, with over 30% of its population already vaccinated at the time of this publication.⁵

In a recent study (yet to be peer-reviewed), 514 Israeli health-care workers were analyzed for immunogenicity 21 days after receiving their first vaccination dose.⁶ In reaction to dose one, patients with prior COVID-19 infections had neutralizing antibodies at an order of magnitude (almost tenfold) higher than those with no evidence of prior disease.

An even more compelling observation was after a single vaccine dose, patients who previously had COVID-19 but no longer presented evidence of antibodies (IgG negative) at the beginning of the study still exhibited a similar antibody response exponentially higher than those patients with no history of prior infection.

Further studies should be conducted to validate and expand these findings as this may have consequences for vaccination policy regarding individuals previously infected with COVID-19. This is especially important at a time when vaccine scarcity is an issue and creating a protocol regarding single- versus double-dose effectiveness in mass populations is being heavily debated.

Natural immunity and vaccine effectiveness against COVID-19 variants

Judging vaccine effectiveness now becomes a more difficult task because of viral variants. Manaus, Brazil, is currently seeing a resurgence of the virus where herd immunity should have already been reached due to high seroprevalence in the population.⁷One theory that warrants further testing is that new variants may have acquired mutations that are facilitating immune evasion.

In a recent study, it was shown that the South African variant of the virus was able to escape neutralization when tested with convalescent plasma from patients infected by the parent COVID-19 virus strain.⁸ In yet another study performed recently by Moderna, serum from vaccinated individuals showed an ability to effectively neutralize the South African variant, but at the cost of a sixfold reduction in neutralizing antibodies in GMTs.⁹

An argument has been made that these pessimistic views regarding the variants are nothing more than in vitro outcomes and don’t cover all the bases in terms of humoral and cell-mediated immune response. Yet the latest results from the Novavax phase 3 trials unfortunately confirm that the variants are indeed showing evidence of immune evasion and that other elements of the immune response, such as T-cell mediation, aren’t playing the active role that we had hoped.

Against the UK variant of the virus, the Novavax vaccine was showing almost 90% effectiveness, which is similar to its mRNA vaccine counterparts. However, in South Africa, where 90% of trial patients were confirmed with the South African variant, efficacy of the vaccine dropped to 60% in preventing mild, moderate, and severe disease.¹⁰ As the Novavax vaccine also targets the spike protein and has similar rates of effectiveness against the parent wild-type and UK strains, it is reasonable to assume that the mRNA vaccines would be similarly less effective at preventing disease against the South African strain.

Moderna and Novavax have stated they are formulating a new vaccine booster targeting these variants. Paradoxically, the selective pressures of the vaccine may accelerate the emergence of further variants that could result in total immune escape.¹¹ Masking and social distancing remain effective strategies to reduce viral transmission in light of uncertainties about vaccine effectiveness.¹²

To summarize:

Vaccines are currently displaying evidence of greater antibody production in comparison to convalescent serum from patients with previous infection.
Patients previously exposed to COVID-19 may experience even greater benefit from vaccination.
Some mutant variants are showing an ability to evade neutralization in convalescent plasma from wild-type strains. Vaccines, though less effective against many variants, still currently exhibit evidence of neutralization. Modified versions of the vaccine will likely be needed to address mutations that enhance immune evasion.

Related articles

Editor’s note: This article originally appeared in Perio-Implant Advisory, a chairside resource for dentists and hygienists that focuses on periodontal- and implant-related issues. Perio-Implant Advisory is part of the Dental Economics and DentistryIQ network. To read more articles, visit perioimplantadvisory.com and subscribe at this link.

References

Ibarrondo FJ, Fulcher JA, Goodman-Meza D, et al. Rapid decay of anti–SARS-CoV-2 antibodies in persons with mild COVID-19. N Engl J Med. 2020;383(11):1085-1087. doi:10.1056/NEJMc2025179
Garcia-Beltran WF, Lam EC, Astudillo MG, et al. COVID-19-neutralizing antibodies predict disease severity and survival. Cell. 2020;184(2):476-488.e11. doi:10.1016/j.cell.2020.12.015
Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and T_H1 T cell responses. Nature. 2020;586(7830):594–599. doi:10.1038/s41586-020-2814-7
Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021; 384(5):403-416. doi:10.1056/NEJMoa2035389
TOI Staff. Over 3 million receive 1st vaccine shot, but COVID outbreak still raging. The Times of Israel. January 31, 2021. Accessed February 3, 2021. https://www.timesofisrael.com/over-3-million-receive-1st-vaccine-shot-but-covid-outbreak-still-raging/
Jabal KA, Ben-Amram H, Beiruti K, et al. Impact of age, gender, ethnicity and prior disease status on immunogenicity following administration of a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from Israeli healthcare workers, December–January 2020. medRxiv. Published online: January 31, 2021. doi:https://doi.org/10.1101/2021.01.27.21250567
Sabino EC, Buss LF, Carvalho MPS, et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet. 2021;397(10273):452-455. doi:10.1016/S0140-6736(21)00183-5
Cele S, Gazy I, Jackson L, et al. Escape of SARS-CoV-2 501Y.V2 variants from neutralization by convalescent plasma. medRxiv. Published online: January 26, 2021. doi:https://doi.org/10.1101/2021.01.26.21250224
Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv. Published online: January 25, 2021. doi:https://doi.org/10.1101/2021.01.25.427948
Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK phase 3 trial. News release. Novavax. January 28, 2021. Accessed January 28, 2021. https://ir.novavax.com/node/15506/pdf
Andreano E, Piccini G, Licastro D, et al. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. bioRxiv. Published online: December 28, 2020. doi:https://doi.org/10.1101/2020.12.28.424451
Moore JP, Offit PA. SARS-CoV-2 vaccines and the growing threat of viral variants. JAMA. Published online: January 28, 2021. doi:10.1001/jama.2021.1114

Christopher H. Jen Kin, DDS, is a general dentist in Pacifica, California, who is currently on staff in the surgery department at Mills-Peninsula Medical Center in Burlingame, California. Dr. Jen Kin earned his DDS degree at the University of the Pacific in San Francisco. He is a fellow in the International Congress of Oral Implantologists as well as an associate fellow in the American Academy of Implant Dentistry.