Does infection with or #vaccination against SARS-CoV-2 lead to lasting immunity ? - The Lancet Respiratory Medicine
Conclusions and future outlook
In this Personal View, we have evaluated evidence on the adaptive immune response to SARS-CoV-2 infection and vaccination, and discussed the relative contributions of humoral and cell-mediated immunity in providing protection against reinfection. Although the immune correlates of protection are ill-defined, neutralising antibodies and functional T-cell responses are often used to infer the robustness of the immune response to SARS-CoV-2 challenge.
Upon natural infection, the T-cell-mediated response appears to be targeted across a larger variety of epitopes than the humoral response, and hence might be more durable to genetic changes in key immunogenic viral epitopes. Nonetheless, the neutralising antibody response also comprises a key aspect of protection against reinfection. Coordination between the two types of adaptive immune response is likely to be important to mitigate the most severe consequences of infection. Populations of specific memory B cells and T cells remain stable or even increase in size many months after SARS-CoV-2 exposure, which might reduce the likelihood of severe disease upon reinfection. The available evidence suggests that reinfection could occur within 5–12 months of a primary infection and is more likely in individuals who are seronegative for IgG antibodies. Interventions to inhibit transmission of SARS-CoV-2 might be required even in places where the herd immunity threshold has been reached naturally or artificially, and observed increases in severity and transmissibility will further drive the imperative for localised or national non-pharmaceutical interventions.
Compared with the immune response to natural infection, vaccination elicits a response of greater magnitude and higher specificity, largely focused on the RBD. Increasing evidence of reduced neutralisation and vaccine effectiveness against emerging variants, alongside emerging data on breakthrough infections, suggests that vaccines will need to be updated in the short-to-medium term. Such updates will be greatly aided by further investigation of vaccine immune correlates of protection. Since completing our literature search on July 26, 2021, several key reports have been published that encourage cautious optimism. For instance, a prospective cohort study of the Scottish population (2·57 million people) showed that during the winter of 2020–21 (the peak of the pandemic), among individuals who had received one dose of either BNT162b2 or ChAdOx1 nCoV-19 vaccine, only 1196 were admitted to hospital or died due to SARS-CoV-2 infection (<0·1% of the cohort). These findings agree with those from a large study of US health records, which showed that two-dose vaccine (BNT162b2) effectiveness against hospital admission following infection with the delta variant remains at 93% up to 6 months after second-dose vaccination, despite waning effectiveness against infection (from 88% in the first month after the second dose to 47% after 5 months). New data also show that the odds of having long-lasting symptoms (≥28 days post-infection) is halved among those who received their second dose of either BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273 at least 28 days previously, compared with unvaccinated individuals (odds ratio 0·51).
Ultimately, the duration of protective immunity from natural infection and from vaccination will determine the frequency of outbreaks (eg, annual, biennial, or more sporadic) and the burden on health-care systems of symptomatic disease, and in turn shape the public health policies of nations around the world in the years to come.