Viruses mutate frequently evolving into new variants and strains over time. Antigenic drift is the process of random genetic mutations of an infectious agent resulting in minor changes in proteins called antigens. These copying errors occur when the virus replicates. Over time, these mutations can result in changes in the virus’ surface antigens, such that the mutated virus that looks significantly different from the original virus can evade the immune response generated by the host’s body against the original virus. Antigenic drift is one of the primary reasons why flu vaccines are updated every year, to keep up with the mutating influenza virus.1

Multiple variants of SARS-CoV-2 have been documented in the United States and globally during the COVID-19 pandemic. As of January 5th, 2022, there are 5 variants of concern (VOCs) spreading globally which are the Alpha Variant (first detected in the UK, B.1.1.7), the Beta Variant (first detected in South Africa, B.1.351), the Gamma Variant (first detected in Brazil, P.1), the Delta Variant (first detected in India, B.1.617.2) and the Omicron Variant (first detected in South Africa, B.1.1.529).2 All these VOCs spread more easily from person to person than the original Wuhan strain.3,4 However, the Delta and Omicron variants have more mutations on the Spike protein, including the receptor binding domain (RBD). These new mutations increase transmissibility compared to the original virus and other VOCs. In particular, data indicate that Omicron may be ten times more infectious than the original SARS‐CoV‐2 virus and twice as infectious than the Delta variant.5

Antibodies to these variants continue to be detected by immunoassays. Most immunoassays use the full-length spike protein or nucleocapsid protein. Generally, our body elicits a polyclonal immune response against the virus upon infection or vaccination. This means we produce antibodies against various antigenic domains (epitopes) of the virus. The genetic changes that the virus acquires over time are largely point mutations. Even if a point mutation compromises one epitope, our body still produces antibodies against all other epitopes, which can be detected by antibody-based detection methods (immunoassays). Overall, the sensitivity and specificity of immunoassays due to such point mutations should not be compromised. However, this is not clear with the Omicron variant as it has more mutations on the Spike protein than previous VOCs. Therefore, more studies are required to assess the impact on current serological assays.5

Novel technologies such as NGS, allow for an effective and unbiased way to identify new coronavirus strains rapidly; they can also detect mutations that can impact vaccine efficacy. Furthermore, data suggest that antibodies generated through currently authorized vaccines recognize these variants and generate an appropriate immune response. As antibody titers are reduced after 6 months of vaccination, boosters are required to maintain protection against all the VOCs including Omicron.6,7 In addition, a recent study has showed that the risk of hospitalization increases in the unvaccinated population infected with the Delta variant.8 Currently, studies are underway to better understand the rate of hospitalization and deaths with the Omicron variant.

In vitro diagnostic companies, pharma industries, and government agencies are vigilant and continue to monitor these variants and studies are underway to understand how variants can impact vaccine efficacy and detection methods.

References

  1. Pfizer. How Do Viruses Mutate and What it Means for a Vaccine? Accessed January 5th, 2022.

2. WHO. Tracking SARS-CoV-2 variants. Accessed January 5th, 2022.

3. CDC. What you need to know about variants. Accessed January 5th, 2022.

4. Haque A, Pant AB. Mitigating Covid-19 in the face of emerging virus variants, breakthrough infections and vaccine hesitancy. Journal of Autoimmunity. 2022;127:102792.

5. Thakur V, Ratho RK. OMICRON (B.1.1.529): A new SARS-CoV-2 variant of concern mounting worldwide fear. J Med Virol. 2021.

6. Carreño  JM, Tcheou J, Singh G et al.Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature. 2021.

7. Padoan A, Cosma C, Bonfante F, et al. Neutralizing antibody titers six months after Comirnaty vaccination: kinetics and comparison with SARS-CoV-2 immunoassays. Clin Chem Lab Med. 2021.

8. Twohig KA, Nyberg T, Zaidi A, et al. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study. Lancet Infect Dis. 2022;22(1):35-42.

 

Maite Sabalza, PhD, and Iswariya Venkataraman, PhD, scientific affairs at EUROIMMUN US, a PerkinElmer company.

 

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