Evaluation of Waning of SARS-CoV-2 Vaccine–Induced Immunity

Abstract

ImportanceEstimates of the rate of waning of vaccine effectiveness (VE) against COVID-19 are key to assess population levels of protection and future needs for booster doses to face the resurgence of epidemic waves.ObjectiveTo quantify the progressive waning of VE associated with the Delta and Omicron variants of SARS-CoV-2 by number of received doses.Data SourcesPubMed and Web of Science were searched from the databases’ inception to October 19, 2022, as well as reference lists of eligible articles. Preprints were included.Study SelectionSelected studies for this systematic review and meta-analysis were original articles reporting estimates of VE over time against laboratory-confirmed SARS-CoV-2 infection and symptomatic disease.Data Extraction and SynthesisEstimates of VE at different time points from vaccination were retrieved from original studies. A secondary data analysis was performed to project VE at any time from last dose administration, improving the comparability across different studies and between the 2 considered variants. Pooled estimates were obtained from random-effects meta-analysis.Main Outcomes and MeasuresOutcomes were VE against laboratory-confirmed Omicron or Delta infection and symptomatic disease and half-life and waning rate associated with vaccine-induced protection.ResultsA total of 799 original articles and 149 reviews published in peer-reviewed journals and 35 preprints were identified. Of these, 40 studies were included in the analysis. Pooled estimates of VE of a primary vaccination cycle against laboratory-confirmed Omicron infection and symptomatic disease were both lower than 20% at 6 months from last dose administration. Booster doses restored VE to levels comparable to those acquired soon after the administration of the primary cycle. However, 9 months after booster administration, VE against Omicron was lower than 30% against laboratory-confirmed infection and symptomatic disease. The half-life of VE against symptomatic infection was estimated to be 87 days (95% CI, 67-129 days) for Omicron compared with 316 days (95% CI, 240-470 days) for Delta. Similar waning rates of VE were found for different age segments of the population.Conclusions and RelevanceThese findings suggest that the effectiveness of COVID-19 vaccines against laboratory-confirmed Omicron or Delta infection and symptomatic disease rapidly wanes over time after the primary vaccination cycle and booster dose. These results can inform the design of appropriate targets and timing for future vaccination programs.

Estimating SARS‐CoV‐2 infections and associated changes in COVID‐19 severity and fatality

“…Waning of vaccine protection during the ancestral and Alpha phases is not considered; indeed, ancestral lineages were replaced by the Alpha variant a few weeks after the start of the vaccination campaign in Italy, and the waning of vaccine protection estimated in the literature during dominance of the Alpha variant is negligible 26,33 . Accordingly, we consider variant‐specific average durations of protection after two doses of vaccine and after a booster dose 34 . Shorter and longer durations of vaccine protection are explored in the sensitivity analyses (Table S4).…”

Poor durability of the neutralizing response against XBB sublineages after a bivalent mRNA COVID‐19 booster dose in persons with HIV

“…[6][7][8] To date, the neutralizing response remains the most widely used correlate of protection from COVID-19, 9 and some reports showed that the levels of neutralizing antibodies (nAbs) as well as vaccine efficacy tend to wane over time from infection or vaccination. [10][11][12] Nevertheless, the proportion of vaccinated individuals and people who experienced natural infection(s) is constantly increasing with a demonstrated benefit of hybrid immunity (infection plus vaccination-driven immunity) in neutralizing SARS-CoV-2. 12,13 It is a matter of debate to whom the updated XBB vaccine shot should be administered, 4,14 nevertheless, the target population for vaccination certainly includes elderly people and severely immunocompromised individuals.…”

Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain

“…Although mRNA vaccines (Moderna mRNA-1273; Pfizer-BioNTech BNT162b2) induce durable germinal center B cells (GCB) responses for at least 6 months 6–9 , the serum neutralizing antibody responses wane within 3 to 6 months and decline further by 8 months, with an estimated half-life of approximately 60 days 10–12 . Waning humoral antibody and emergence of resistant, highly transmissible variants correlate with an increased frequency of breakthrough infections in vaccinated individuals 13,14 .…”