COVID-19 vaccine-induced Immunity beyond the Variants

COVID – 19 is a public-health threat produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It belongs to the coronaviridae family, and the genus beta-coronaviruses. As of November 30th, 2021, it had caused 262 million infections and 5.2 million deaths, and vaccination is one approach to prevent people against COVID -19.

The World Health Organization (WHO) identified Pfizer/BioNTech as the first vaccine for emergency use one year after the first case of COVID-19. The WHO then added eight more vaccines to its list of emergency vaccines. Vaccines are substances that “train” the immune system how to fight infections (They help the immune system to create memory against antigens that they have actively not encountered, in that with the actual encounter a more robust and specific immune response is elicited). Nucleic acid vaccines (Pfizer/BioNTech, Moderna, and Vaxveria), whole inactivated virus vaccines (Sinovac, and Sinopharm), adenoviral vectors (AstraZeneca, J&J), and protein subunit vaccines (AstraZeneca, J&J) are the four primary types of COVID-19 vaccines. Observational studies have revealed that many vaccination types provide some protection against infection and serious disease.

SARS – CoV-2, like any other virus, has mutated and changed some of its features throughout time, resulting in new variants. The emergence of several SARS-CoV-2 variants with various mutations has ramifications for vaccination efficacy, disease severity, and transmissibility. The Alpha, Beta, Gamma, Delta, and the recently discovered Omicron are among the variants of concern (VOC). The Alpha (B.1.1.7) variant, which was originally discovered in the United Kingdom and was declared a VOC by the World Health Organization in December 2020, features ten mutations in the spike protein. The spike protein of the Beta (B.1.351) variant, which was originally discovered in South Africa and classified a VOC in December 2020, includes 11 mutations.

The Gamma (P.1) variant that was first detected in Brazil and designated a VOC in January 2021 has 12 mutations in the spike protein. The Delta (B.1.617.2) variant that was first detected in India and designated a VOC in May 2021 has 9 mutations in the spike protein. Then the recently identified Omicron (B.1.1.529) variant by South African scientists has 30 AA substitutions, 3 deletions and 1 insertion in the spike protein and was designated a VOC in November 2021.  Mutations of concern are those that affect the viral spike protein and affect the binding affinity with the Angiotensin – converting enzyme 2 (ACE 2) receptor. Also, these VOCs have a shared E484K mutation in the region bound by neutralizing antibodies hence affects antibody binding capacity. 

The effect of these mutations on neutralizing antibody titers has been studied extensively. The Alpha variant, for example, has a mild influence on neutralizing antibody titers, whereas the Delta and Gamma variants have a more dramatic effect on antibody neutralization. This is because the variants escapes spike specific neutralizing antibodies as a result of the mutations in their spike protein. B cells recognizes antigens via a receptor in their cognate native form, in this instance B cell receptors will recognize the viral spike protein in its native form. Any alterations to the spike protein could impair its identification by B cell receptors, affecting the development of spike protein-specific neutralizing antibodies.

Despite the partial escape of the viral variants to the spike-specific neutralizing antibodies, viral variants can only cause mild or asymptomatic disease in fully vaccinated individuals. This is because even low levels of neutralization antibodies may protect people from severe forms of COVID-19 and also the role of the T cells. T cells recognize small peptides processed from the viral spike protein when presented by a specific HLA type. This means Vaccine–Induced Spike – specific T cells do not recognize the entire spike protein but rather small peptides from the different regions of the spike protein and hence are multispecific. Therefore, variants are unable to fully escape Spike–specific T cells. Although some mutations might alter the T cells specificity, it will be hard to escape the whole repertoire of Spike- specific T cells. Vaccines might not prevent infection from new variants but will protect us from severe disease outcomes.

The writer; Fortunate Ahumuza is a Biochemist and Immunologist with interests in Vaccinology
Email: ahumuzafortunate03@gmail.com