SARS-CoV-2 elicits non-sterilizing immunity and evades vaccine-induced immunity: implications for future vaccination strategies

Abstract

Neither vaccination nor natural infection result in long-lasting protection against SARS-COV-2 infection and transmission, but both reduce the risk of severe COVID-19. To generate insights into optimal vaccination strategies for prevention of severe COVID-19 in the population, we extended a Susceptible-Exposed-Infectious-Removed (SEIR) mathematical model to compare the impact of vaccines that are highly protective against severe COVID-19 but not against infection and transmission, with those that block SARS-CoV-2 infection. Our analysis shows that vaccination strategies focusing on the prevention of severe COVID-19 are more effective than those focusing on creating of herd immunity. Key uncertainties that would affect the choice of vaccination strategies are: (1) the duration of protection against severe disease, (2) the protection against severe disease from variants that escape vaccine-induced immunity, (3) the incidence of long-COVID and level of protection provided by the vaccine, and (4) the rate of serious adverse events following vaccination, stratified by demographic variables.

Responses to Common Misconceptions Relating to COVID-19 Variant-Adapted mRNA Vaccines

“…Although the impact on symptomatic disease and transmission was an additional benefit of COVID-19 vaccines during the early stages of the pandemic, owing to ongoing viral evolution, vaccination strategies with these updated vaccines are likely to focus on the prevention of severe disease [ 86 ]. As protection offered by natural infection or vaccination wanes over time, it is important to keep up to date with COVID-19 vaccinations.…”

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

“…Our characterization of neutralizing function showed a greatly reduced neutralizing capacity from WT to Omicron variants as was expected from previous reports showing the great immune evasion potential of the Omicron strain (1, 3-5, 8-13). Because neither vaccination nor past infection could be shown to confer sterilizing immunity, serum-neutralizing activity cannot solely be regarded as the key immune function (25,(41)(42)(43). Thus, looking at other parts of immune function such as binding affinity can provide insights crucial for understanding immunity against SARS-CoV-2 and preventing (severe) disease.…”

Study of optimal vaccination strategies for early COVID-19 pandemic using an age-structured mathematical model: A case study of the USA

“…In addition, they considered specific vaccine availability in the USA. This aspect differentiates this study from many others where the vaccination pace is generally a constant proportion of the population [ 32 , 34 , 35 ]. The authors analyzed in a clever way all possible vaccine allocation strategies, instead of a few strategies.…”

“…For instance, many different simulations can be performed, allowing the investigation of various factors under a variety of scenarios where uncertainty plays an important role. Some studies have used simple SIR or SEIR models without age-group structure which is a crucial factor for optimal vaccination [ 32 – 35 ]. In [ 36 ] the authors formulated an optimal control problem to design vaccination schedules taking into account the number of disability-adjusted years of life lost.…”