How have independent meta-analyses and systematic reviews evaluated mRNA and viral-vector vaccine performance and waning immunity?
Executive summary
Independent systematic reviews and meta-analyses consistently find that mRNA COVID-19 vaccines produce higher peak neutralizing antibody responses and higher initial effectiveness than many other platforms, but protection against infection wanes substantially within months while protection against severe disease remains more durable (e.g., pooled VE ~46–56% vs. hospitalization for recent XBB‑adapted mRNA boosters in older adults) [1] [2] [3]. Meta-analyses and modelling papers also report that viral‑vector vaccines tend to produce lower peak antibody titers but sometimes slower measured declines in certain antibody metrics and stronger cellular signatures that may stabilize protection differently over time [1] [4] [5].
1. “Higher peaks, faster fall: what pooled antibody data say”
Systematic reviews that pooled neutralizing‑antibody studies show mRNA platforms achieve higher mean peak titers than other vaccine types, a finding driving many conclusions that mRNA vaccines give stronger early protection; those same reviews note relatively few direct comparisons with viral‑vector vaccines in the primary data, limiting the certainty of cross‑platform claims [1]. A large meta‑regression and modelling analysis further quantifies platform differences in waning: after peaking, mRNA and heterologous series show faster multi‑fold declines in nAb titers over 90‑day intervals than viral‑vector vaccines, which in one model dropped about 1.4‑fold every 90 days (95% CrI 1.1–1.9) [4].
2. “Effectiveness vs. outcomes: infection drops, hospital protection holds”
Meta-analyses of clinical effectiveness emphasize divergence between VE against any infection and VE against severe outcomes: effectiveness against symptomatic or any infection declines rapidly with time and with immune‑evasive variants, while protection against hospitalization and death is more sustained. For example, pooled estimates from observational studies of XBB‑adapted mRNA boosters showed around 56% (95% CI, 51–60) effectiveness against hospitalization in adults ≥65 in cohort analyses, and other pooled analyses returned mid‑range VE against hospitalization for adults overall [2] [3].
3. “Viral vectors: steadier slopes and cellular advantages — with caveats”
Reviews of viral‑vector platforms document strengths and limits: vectors produce robust cellular responses that can confer cross‑reactive protection and sometimes show slower measured declines in certain antibody metrics, but pre‑existing anti‑vector immunity and heterogeneity across vectors complicate generalisation [6] [7] [5]. The Nature Communications meta‑analysis model found viral‑vector titers declined more slowly in a specific window, but the authors caution that neutralizing titers are an imperfect correlate for protection against severe disease [4].
4. “Observational meta‑analyses, modelling and the variant problem”
Systematic reviews repeatedly stress context dependence: waning estimates conflate time since vaccination and immune escape from new variants, and observational VE meta‑analyses must account for shifting variant dominance, prior infection (hybrid immunity), and study design differences — limitations acknowledged across reviews and models [1] [8] [9]. Independent consortia pooling large numbers of studies concluded updated mRNA boosters gave meaningful but partial protection against hospitalization in the XBB era, underscoring variant impact on apparent waning [3] [2].
5. “Where meta‑analyses disagree and why”
Disagreements among reviews trace to different endpoints (nAb titers vs. symptomatic infection vs. hospitalization), variable follow‑up windows, limited head‑to‑head trials, and under‑representation of some platforms in immunogenicity studies; several reviews explicitly note sparse direct comparisons of viral vectors versus mRNA for neutralization decay [1] [4]. Modellers warn that antibody waning curves’ shape matters epidemiologically and that current empirical data are insufficiently granular to settle which platform gives longer functional protection in every context [10].
6. “Implications for policy, research and public discourse”
Independent syntheses uniformly argue for layered conclusions: mRNA vaccines give higher early protection and remain strongly protective against severe disease, but waning of protection against infection is real and exacerbated by immune‑evasive variants; viral vectors may offer complementary immunological features but need more comparative data [1] [3] [4]. Reviews call for standardized, head‑to‑head immunogenicity studies, longer longitudinal cohorts that capture hybrid immunity, and clearer reporting so meta‑analyses can better separate waning from immune escape [1] [9].
Limitations: available sources do not mention a single definitive, platform‑agnostic timeline for “full” waning to zero effectiveness; all quantitative claims above are drawn from the cited meta‑analyses, models and pooled observational studies [1] [4] [3] [2].