**4.1 Impact of emergence of new variants on vaccine**

Since the beginning of the pandemic, VOC having selective advantage of more transmissibility and resistance to natural or vaccine induced immunity have been evolving and supplanting previously circulating strains [43, 84]. The emergence of these VOC affects the effectiveness of vaccines in both partially and fully immunized individuals [43]. In vitro studies demonstrated lower neutralization capacity against all VOC compared to ancestral strains [41, 85, 86]. Based on evidence available for all vaccine types, partially immunized individuals have a lower degree of protection against symptomatic infection, moderate disease, and probable transmission with Delta VOC than Alpha VOC. In general, the vaccine effectiveness for all variants against symptomatic disease was much lower than those reported against severe diseases. The fully immunized individuals confer nearly equivalent protection for all outcomes against Alpha to that of Delta variants [43]. **Table 1** summarizes the results of vaccine effectiveness by type of vaccine, outcome, and VOC.

The emergence of new vaccine-resistant variants may necessitate the development of modified vaccines based on new sequences to prevent the prolonged circulation of vaccine-resistant variants [84]. It is important to conduct studies of these modified vaccines to determine its efficacy in developing a neutralizing immunological response against vaccine-resistant variants. This research is important despite the deployment of these newer vaccines not required until there is evidence of failure of current vaccines. Once the modified vaccines are introduced the molecular and immunological determinants of viral adaptation will necessitate to repeat the cycle of monitoring for even newer variants that might require further modifications in the antigenic sequence in vaccines.

Like vaccines, the viral adaptations seen against the monoclonal antibody therapy

can complicate the deployment of these treatments at large scale in the general


### **4.2 Impact of emergence of new variants antibody therapy**

### **Table 1.**

*Vaccine effectiveness of two dose of vaccines against symptomatic infection and severe disease caused by non-VOCs, alpha, and Delta VOCs.*

### *Biological Determinants of Emergence of SARS-CoV-2 Variants DOI: http://dx.doi.org/10.5772/intechopen.104758*

population [55]. The initial widespread use of Bamlanivimab as a single therapy and later removal due to epidemiologic trend further provides evidence for judicious use of monoclonal antibody therapy [87]. The usage of cocktail of antibodies should in theory reduce the probability of random selection of resistant variants however it does not totally remove this possibility [55]. This combined with monoclonal antibodies not preventing transmission, not providing immediate cure, lacking durable immunity, and potentially leading to antibody strains with some cross-resistance against vaccine or natural-acquired immunity suggests the need for caution before widespread usage of monoclonal antibody therapy [41, 55]. Increasing the scale of surveillance for mutations along with research into monoclonal antibodies against newer antigens should be adopted if the scale of use of monoclonal antibody has to be expanded [55].

Thus, the determinants of emergence of SARS-CoV-2 variants necessitates the inclusion of epidemiological, evolutionary, clinical, animal, and in vitro data related to changing antigenic sequences, vaccine and monoclonal antibody efficacy in the decision making of which antigens to be included in vaccines or targeted for therapy [84]. Lastly, it is important to recognize the limitations of the concepts presented in this chapter. This is a prospective chapter piece using concepts and theoretical ideologies commonly attributed to variant emergence. The inclusion of the determinants presented are a combination of expert knowledge on behalf of the authors and a scoping literature review conducted on SARS-CoV-2 and its current variants, therefore, this chapter is not meant to replace a systematic review.
