Implications of the COVID Vaccine in Clinical Practice

Since February 2020, U.S. oral health professionals and patients have been addressing the health implications of SARS-CoV-2, a novel coronavirus that manifests as COVID-19 disease. As of this writing, COVID-19 has infected more than 17.7 million Americans and killed more than 316,000.¹ According to the World Health Organization, more than 76.2 million cases of COVID-19 have been confirmed globally (by presstime), with 1.7 million deaths attributed to the virus.² While most individuals are aware of safety measures — such as frequent handwashing, social distancing and wearing masks — cases of COVID-19 continue to rise at an alarming rate. Oral healthcare personnel can use guidance from the U.S. Centers for Disease Control and Prevention (CDC),³ American Dental Association (ADA),⁴ American Dental Hygienists’ Association (ADHA),⁵ Occupational Safety and Health Administration,⁶ and the Organization for Safety Asepsis and Prevention⁷ to continue providing safe care and control infectious transmission.

Despite mitigating measures, the pandemic continues to challenge the nation — indeed, the world — and will remain devastating until vaccines become widely available and enough people have been immunized to create herd immunity. This paper will provide an overview of emerging coronavirus vaccines and discuss the implications for oral health professionals.

Multiple companies throughout the world are developing vaccines to protect against COVID-19. Various approaches are being used, including mRNA vaccines, protein subunit vaccines and vector vaccines. None of these contain the live virus, so these vaccines cannot infect individuals with COVID-19.

Vaccines using mRNA technology have been studied for use against other diseases, including the flu, Zika, rabies and cytomegalovirus. With this technology, material from the SARS-CoV-2 virus issues instructions for cells to make a harmless protein that is unique to the virus, known as a spike (S) protein. Once cells make copies, the genetic material from the spike protein is destroyed from the vaccine. The immune system will recognize this protein as foreign, and T-lymphocytes and B-lymphocytes will build an immune response to fight the virus should an infection occur.⁸ The S protein is the most likely target antigen for long-term immune response and vaccine design for COVID-19.⁹ The rapid pace of vaccine development is attributed to prior knowledge of the S protein and its role in immunity and coronavirus pathogenesis.¹⁰

Protein subunit vaccines include harmless proteins of the virus that causes COVID-19, rather than the entire virus. Similar to the effect of the mRNA vaccine, the immune system will recognize these proteins as foreign and develop antibodies to fight the virus if infected.⁸

Vector vaccines contain a weakened version of a live virus that, while distinct from SARS-CoV-2, has genetic material from SARS-CoV-2 inserted — hence the name viral vector. Once the vector enters cells, genetic material provides instructions to make copies of a protein that is unique to the COVID-causing virus. In this way, T- and B-lymphocytes are created to fight the virus should infection occur.⁸

mRNA-1273

In partnership with the National Institute of Allergy and Infectious Diseases, Moderna has developed a vaccine¹¹ that utilizes the stabilized SARS-CoV-2 spike immunogen (or S-2P), which mediates attachment and entry of the virus into host cells. Research suggests mRNA-1273 generates a robust immune response to the SARS-CoV-2 S protein.¹⁰

The clinical trial for mRNA-1273 enrolled 30,000 subjects, who were assigned to a single blind randomized 1:1 trial (meaning, participants had a 50% chance of receiving mRNA-1273 or the placebo).¹² Both were delivered intramuscularly to the upper arm on Day 1 and Day 29 of the trial.¹³ An independent data and safety monitoring board evaluated 95 cases of COVID-19 among study participants. Of these, 90 infections were in subjects who had received the placebo, while five were in participants who had received mRNA-1273.¹⁴ These results demonstrate the vaccine has a 94.5% efficacy.^14,15

At presstime, the Moderna vaccine had just received emergency use authorization (EUA) from the U.S. Food and Drug Administration, following closely behind the EUA granted to the BNT162b2 vaccine developed by BioNTech and Pfizer. An EUA is a mechanism to facilitate the availability of medical measures, such as vaccines, during a public health crisis.¹³ Mobilization is underway for widespread vaccination, and it is anticipated that 20 million doses of mRNA-1273 will be developed by the end of 2020.¹⁶ It is important to note that mRNA-1273 needs to be stored at -20° Celsius (-4° Fahrenheit).¹⁷ Once thawed, the vaccine will tolerate normal refrigeration of 2° to 8° Celsius (35° to 46° Fahrenheit) for up to 30 days.¹⁸

AZD1222

The AZD1222 vaccine is being developed through a joint effort between the University of Oxford and Vaccitech.¹⁹ AstraZeneca will manufacture and distribute it. Unlike AstraZeneca’s mRNA-1222 vaccine, AZD1222 uses a viral vector to introduce the S protein material of SARS-CoV-2 into the patient. Once the immune system recognizes this genetic material, the individual will develop the S protein, thus creating immunogenicity.²⁰ Results from the AZD1222 vaccine vary, depending on the dosing regimen. Two schedules for the vaccine were tested: the first being a half dose, followed by a full dose dispensed 30 days later. This method demonstrated 90% immunogenicity, as compared to its two full-dose counterpart, which was 62% effective when administered 30 days apart.¹⁹ More than 11,000 participants were enrolled in the study, which showed a combined efficacy of 70% from the two dosing regimens.²⁰

If it receives EUA approval, AstraZeneca will ramp up production of the vaccine, with the goal of providing up to 3 billion doses in 2021. A noticeable difference between mRNA-1273 and AZD1222 is that AZD1222 can be handled similarly to other vaccines. It is viable at normal refrigeration temperatures, and has a shelf life of up to six months.¹⁷

AD26.COV2.S

The AD26.COV2.S vaccine was developed by Jansen Pharmaceutical, a subsidiary of Johnson & Johnson, in conjunction with the Biomedical Advanced Research and Development Authority.²¹ This vaccine uses the Advac vaccine platform, which is proprietary to Johnson & Johnson. Advac technology utilizes a genetically modified adenovirus embedded with a full-length spike protein S-2P.²² This vaccine differs from the first two in that early results demonstrate 98% of the participants had neutralizing antibodies with a single injection, rather than two doses.²³

At presstime, AD26.COV2.S was being studied with the help of 60,000 participants and is in Phase III of the research process. Once the study has reached the endpoint, it is anticipated Johnson & Johnson will apply for an EUA. If approved, it is expected to provide the vaccine on a nonprofit basis for emergency pandemic use.²⁴

BNT162b2

Developed by BioNTech and Pfizer, BNT162b2 was the first COVID-19 vaccine to receive an EUA for use in the United States. This vaccine uses mRNA embedded with the SARS-CoV-2 full-length spike, modified by two proline mutations to lock it in the prefusion conformation and more closely mimic the intact virus, with which the elicited virus-neutralizing antibodies must interact.”²⁵ Participants in the study for BNT162b2 received two injections into the upper arm 21 days apart. Preliminary results for this vaccine demonstrated over 95% immunogenicity for COVID-19.²⁶ The partnership expects to distribute 50 million doses of BNT162b2 by the end of 2020, and up to 1.3 billion doses by the end of 2021.²⁷ Unlike the other vaccines, it requires specialized storage for maximum efficacy. The concentrated vaccine must be stored and transported at -70° Celsius (-94 Fahrenheit). When ready for use, the undiluted concentrate will be thawed and diluted. Once dilution occurs, BNT162b2 has a shelf life of only six hours.¹⁷

OTHER VACCINE CONSIDERATIONS

In testing, side effects were reported for all four of these vaccines at the administered dose or dosages. These were generally tolerable, low-grade reactions. Side effects included mild fever, fatigue, headaches, and pain at the injection site. Although side effects were noted, all were resolved within one to two days.^{11,15,19,20,25} During vaccine trials in the United Kingdom, two cases of severe allergic reaction occurred with the BioNTech/Pfizer vaccine. It should be noted some individuals are predisposed to allergic diathesis or underlying allergic tendencies; for these individuals, caution is advised and vaccine administrators should be prepared to manage these responses.

Ideally, all vaccines that come to market should be capable of inducing a robust response involving both neutralizing antibodies and T-cells that will provide a significant level of protection against COVID-19. The typical vaccine development time frame is 10 to 15 years and involves multiple preclinical and clinical trials. Yet due to the accelerated need associated with this pandemic, the development process and ongoing clinical trials have occurred in less than a year in some cases. As various vaccines advance through the EUA process, the CDC will provide guidance for states to decide how to prioritize immunization. The CDC has suggested healthcare workers and long-term care residents should be among the first to be vaccinated, but ultimately it is up to each state to decide how to allocate their immunization resources.²⁸

Further, vaccine delivery methods and efficacy measures for those most at risk (i.e., older adults) are being addressed. Vaccination as a public health measure protecting vulnerable populations — perhaps including high-dose antigens or using an adjuvant — may need to be investigated for certain segments of the population.²⁹ Additional strategizing and vaccine development will continue, allowing more time to discover if viral mutations impact vaccine efficacy, whether immunity to the vaccine wanes, if boosters are required, and how resources will be provided to ensure equitable access to the vaccines worldwide.³⁰

HERD IMMUNITY

Immunity to a virus or disease occurs via infection and recovery from the disease, or by immunization.³¹ The intent of herd immunity is not to prevent clinical symptoms, but rather to stop further transmission of the disease. Transmission depends on several factors, which include density of the population, population structure, and variations in contact rates across various demographics.³¹ The basic concept is that once a certain percentage of the population is immune, transmission becomes less likely because the potential pool of hosts is reduced.

When a pathogen is particularly virulent, more of the population must be immune to the pathogen in order for herd immunity to occur.³¹ In the case of SARS-CoV-2, hosts may be infectious without displaying symptoms, thereby potentially spreading disease asymptomatically. Estimates for reaching herd immunity vary, as the disease continues to spread globally. Some estimates suggest herd immunity will be reached once 67% of the population achieves immunity to SARS-CoV-2.³¹

IMPLICATIONS FOR ORAL HEALTHCARE

Among the implications of vaccine development is a call by the ADA, ADHA and American Dental Education Association (ADEA) to recognize dental providers — including laboratory technicians and oral health students — as high-risk workers who should be among the first to receive the vaccine.^32–34

In addition, dentists, dental hygienists and dental therapists can play a pivotal role in mitigating COVID-19 by being part of the vaccination response. As highly trained professionals who regularly administer local anesthesia, these team members can expand the medical team’s capacity to administer vaccines and thus reduce the occurrence of COVID-19. To support this concept, a number of key groups, including the Academy of General Dentistry, American Association for Dental Research, ADA, ADHA and ADEA, wrote to the U.S. Department of Health and Human Services asking that dental professionals be allowed to administer vaccines to help control the COVID-19 outbreak.³⁵ The ADA recently passed resolution 91H-2020 recognizing that dentists have the knowledge and skills to administer vaccines.³⁶ At presstime, Oregon was the first state to allow dentists to prescribe and administer vaccines,³⁷ and Connecticut recently authorized dentists and dental hygienists to administer COVID-19 vaccines after completing a training program,³⁸ while Minnesota and Illinois allow dentists to administer flu vaccinations only to adult patients.

Further, dentists, dental hygienists and dental therapists play an important role in educating patients about the importance of vaccination in controlling this pandemic. As healthcare providers, it is incumbent upon dental teams to remain current and deliver accurate information about COVID-19, vaccination availability, the benefits of immunization, and anticipated side effects.

CONCLUSION

In combination with effective mitigation measures, such as wearing masks, maintaining social distancing and frequent handwashing, widespread vaccination offers hope of controlling SARS-CoV-2 transmission. Until vaccines become widely available and herd immunity is established, COVID-19 will continue to challenge the nation and world. As various vaccines receive EUA consideration and approval, investigations of the long-term effects of each vaccine will remain ongoing. At the same time, oral health professionals can help stem the pandemic by educating team members and patients about the importance of being vaccinated, and potentially increasing access to vaccines through immunization in dental settings.

REFERENCES

1. U.S. Centers for Disease Control and Prevention. CDC COVID Data Tracker. Available at: https:/​/​covid.cdc.gov/​covid-data-tracker/​#cases_​casesper100klast7days. Accessed December 10, 2020.
2. World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard. Available at: https:/​/​covid19.who.int/​?gclid=Cj0KCQiAwf39BRCCARIsALXWETyth8Hf0cBQy6sNB6PBRopC_​Jp1mW-vM0G7tX883lYKwuDPBwsrb34aAgeXEALw_​wcB. Accessed December 10, 2020.
3. U.S. Centers for Disease Control and Prevention. Infection prevention and control in dental settings: Current COVID-19 interim guidance. Available at: https:/​/​www.cdc.gov/​oralhealth/​infectioncontrol/​index.html. Accessed December 10, 2020.
4. American Dental Association. Summary of ADA guidance during the COVID-19 crisis. Available at: https:/​/​success.ada.org/​~/​media/​CPS/​Files/​COVID/​COVID-19_​Int_​Guidance_​Summary.pdf. Accessed December 10, 2020.
5. American Dental Hygienists’ Association. ADHA interim guidance on returning to work. Available at: https:/​/​www.adha.org/​resources-docs/​ADHA_​TaskForceReport.pdf. Accessed December 10, 2020.
6. Occupational Safety and Health Administration. COVID-19. Available at: https:/​/​www.osha.gov/​SLTC/​covid-19/​. Accessed December 10, 2020.
7. Organization for Safety Asepsis and Prevention. Coronavirus disease (COVID-19) toolkit. Available at: https:/​/​www.osap.org/​page/​COVID-19. Accessed December 10, 2020.
8. U.S. Centers for Disease Control and Prevention. Understanding how COVID-19 vaccines work. Available at: https:/​/​www.cdc.gov/​coronavirus/​2019-ncov/​vaccines/​different-vaccines/​how-they-work.html?CDC_​AA_​refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fvaccines%2Fabout-vaccines%2Fhow-they-work.html. Accessed December 10, 2020.
9. National Institutes of Health. Phase 3 clinical trial of investigational vaccine for COVID-19 begins. Available at: https:/​/​www.nih.gov/​news-events/​news-releases/​phase-3-clinical-trial-investigational-vaccine-covid-19-begins. Accessed December 10, 2020.
10. Moderna. Clinical study protocol. Available at: https:/​/​www.modernatx.com/​sites/​default/​files/​mRNA-1273-P301-Protocol.pdf. Accessed December 10, 2020.
11. Moderna. A study to evaluate efficacy, safety, and immunogenicity of mRNA-1273 vaccine in adults aged 18 years and older to prevent COVID-19. Available at:https:/​/​clinicaltrials.gov/​ct2/​show/​NCT04470427. Accessed December 10, 2020.
12. National Institutes of Health. Promising interim results from clinical trial of NIH-Moderna COVID-19 vaccine. Available at: https:/​/​www.nih.gov/​news-events/​news-releases/​promising-interim-results-clinical-trial-nih-moderna-covid-19-vaccine. Accessed December 10, 2020.
13. U.S. Food and Drug Administration. Emergency use authorization for vaccines explained. Available at: https:/​/​www.fda.gov/​vaccines-blood-biologics/​vaccines/​emergency-use-authorization-vaccines-explained. Accessed December 10, 2020.
14. Moderna. COVID-19 vaccine (mRNA-12730). Available at: https:/​/​www.modernatx.com/​sites/​default/​files/​content_​documents/​mRNA-1273-Update-11-16-20-Final.pdf. Accessed December 10, 2020.
15. AstraZeneca. AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19. Available at: https:/​/​www.astrazeneca.com/​media-centre/​press-releases/​2020/​azd1222hlr.html. Accessed December 10, 2020.
16. AstraZeneca. AstraZeneca and Oxford University announce landmark agreement for COVID-19 vaccine. Available at: https:/​/​www.astrazeneca.com/​media-centre/​press-releases/​2020/​astrazeneca-and-oxford-university-announce-landmark-agreement-for-covid-19-vaccine.html. Accessed December 10, 2020.
17. Stead Sellers F, Sun LH, Rowland C. What you need to know about the Pfizer, Moderna, and AstraZeneca vaccines. Available at: https:/​/​www.washingtonpost.com/​health/​2020/​11/​17/​covid-vaccines-what-you-need-to-know/​?arc404=true. Accessed December 10, 2020.
18. Moderna vaccine storage requirements enables distribution in rural America: U.S. Official. Available at: https:/​/​www.usnews.com/​news/​top-news/​articles/​2020-11-16/​moderna-vaccine-stability-enables-distribution-in-rural-america-us-official. Accessed December 10, 2020.
19. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOxx1 NCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/​2, single-blind, randomized controlled trial. Lancet. 2020;396:467–478.
20. AstraZeneca. Two different dosing regimens demonstrated efficacy with one showing a better profile. Available at: https:/​/​www.astrazeneca.com/​media-centre/​press-releases/​2020/​azd1222hlr.html. Accessed December 10, 2020.
21. Johnson & Johnson. Johnson & Johnson announces a lead vaccine candidate for COVID-19; Landmark new partnerships with U.S. Department of Health and Human Services: and commitment to supply one billion vaccines worldwide for emergency pandemic use. Available at: https:/​/​www.jnj.com/​johnson-johnson-announces-a-lead-vaccine-candidate-for-covid-19-landmark-new-partnership-with-u-s-department-of-health-human-services-and-commitment-to-supply-one-billion-vaccines-worldwide-for-emergency-pandemic-use. Accessed December 10, 2020.
22. Janssen. Vaccine technology. Available at: https:/​/​www.janssen.com/​infectious-diseases-and-vaccines/​vaccine-technology. Accessed December 10, 2020.
23. Johnson & Johnson. Johnson & Johnson posts interim results from phase 1/​2a clinical trial of its Janssen COVID-19 vaccine candidate. Available at: https:/​/​www.jnj.com/​johnson-johnson-posts-interim-results-from-phase-1-2a-clinical-trial-of-its-janssen-covid-19-vaccine-candidate. Accessed December 10, 2020.
24. Johnson & Johnson. Johnson & Johnson joins other companies in signing a landmark communique on expanded global access for COVID-19. Available at: https:/​/​www.jnj.com/​latest-news/​johnson-johnson-signs-communique-on-expanded-global-access-for-covid-19-vaccines. Accessed December 10, 2020.
25. Walsh E, Frenck RW, Falsey AR, et al. Safety and immunogenicity of two RNA-based COVID-19 vaccine cadidates. N Engl J Med. October 14, 2020. Epub ahead of print.
26. Pfizer. Update: Albert Bourla discusses COVID-19 vaccine efficacy results. Available at: https:/​/​www.pfizer.com/​news/​hot-topics/​albert_​bourla_​discusses_​covid_​19_​vaccine_​efficacy_​results. Accessed December 10, 2020.
27. Pfizer. Albert Bourla discusses our FDA submission. Available at: https:/​/​www.pfizer.com/​news/​hot-topics/​albert_​bourla_​discusses_​our_​fda_​submission. Accessed December 10, 2020.
28. CDC recommends nursing homes and health workers get vaccines first. Available at: https:/​/​www.nytimes.com/​live/​2020/​12/​01/​world/​covid-19-coronavirus?action=click&module=Top%Stories&pgtype=Homepage. Accessed December 10, 2020.
29. Ghaebi M, Osali A, Valizadeh H, Roshangar L, Ahmadi M. Vaccine development and therapeutic design for 2019-nCoV/​SARS-CoV-2: Challenges and chances. J Cell Physiol. 2020;235:9098–9109.
30. Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20:615–632.
31. Randolph HW, Barreiro LB. Herd immunity: Understanding COVID-19. Immunity. 2020;52:737–741.
32. American Dental Association. Letter to Advisory Committee on Immunization Practices. Available at: https:/​/​www.ada.org/​~/​media/​ADA/​Advocacy/​Files/​201120_​cdc_​acip_​covid19_​nosig.pdf. Accessed December 10, 2020.
33. American Dental Hygienists’ Association. Letter to Committee on Equitable Allocation of Vaccine for the Novel Coronavirus, The National Academies of Science, Engineering and Medicine. Available at: https:/​/​www.adha.org/​resources-docs/​ADHA_​Letter_​to_​NASEM_​Committee_​on_​Equitable_​Allocation_​of_​Vaccine.pdf. Accessed December 10, 2020.
34. American Dental Education Association. ADEA Supports Prioritization of COVID-19 Vaccine for Dental Community. Available at: https:/​/​www.adea.org/​Sept2020-COVID19-Vaccine-for-Dental-Community/​?_​zs=B2bUf1&_​zl=pSRG7. Accessed December 10, 2020.
35. COVID-19 Dental Coordination Group. Letter to ADM Brett P. Giroir, MD. Available at: https:/​/​www.agd.org/​docs/​default-source/​advocacy-papers/​prepactdentistvaccinationauthorizationfinal.pdf?sfvrsn=92fe92b9_​0. Accessed December 10, 2020.
36. Solana K. ADA supports efforts allowing dentists to administer vaccines. Available at: https:/​/​www.ada.org/​en/​publications/​ada-news/​2020-archive/​october/​ada-supports-efforts-allowing-dentists-to-administer-vaccines. Accessed December 10, 2020.
37. Oregon dentists are ready to administer COVID-19 vaccine. Available at: https:/​/​decisionsindentistry.com/​2020/​10/​oregon-dentists-ready-administer-covid-vaccine/​. Accessed December 10, 2020.
38. Connecticut Department of Public Health. Order December 7, 2020. Available at: https://portal.ct.gov/-/media/Coronavirus/20201207-DPH-Order-Expanding-Authorized-Professions-to-Administer-Vaccines.pdf. Accessed December 21, 2020.

From Decisions in Dentistry. January 2021;7(1):26—28, 31.