Third vaccine doses could have indirectly averted >100,000 deaths in the USA by reducing transmission of the SARS-CoV-2 Delta variant

Abstract

Background Vaccines have greatly reduced the impact of COVID-19 globally. Unfortunately, evidence indicates that immunity wanes following vaccination, especially with the Delta variant (B.1.617.2). Protection against severe disease and death remain high, but protection against milder disease and infection have dropped significantly. A third booster dose of two-dose vaccines has been approved in several countries to individuals at higher risk of severe disease to protect those individuals, but the benefit to boosting immunity in younger healthy individuals and the effects on transmission are less clear. Methods Here we use relationships between neutralizing antibody titers and vaccine protection against infection and transmission, combined with data on waning and boosting of neutralizing antibody titers to examine the impact of a third dose of the Pfizer vaccine on infection and transmission and its impact on the pathogen effective reproductive number Rt. Findings Eight months of waning reduced protection of the Pfizer vaccine against all infections from 80.0% (95% CI: 77% to 83%) to 60.4% (95% CI: 53% to 67%); a third dose (which increased neutralizing antibody titers 25.9- fold relative to levels after 8 months of waning) increased protection to 87.2% (95% CI: 83% to 91%). Increased protection against infection and transmission from third doses reduced Rt by 21% to 66% depending on vaccine coverage and previous infection and reduced Rt below 1 when vaccination coverage was high or contact rates were well below pre-pandemic levels. Interpretation A third dose of the Pfizer vaccine could reduce transmission of SARS-CoV-2, which would reduce infection in unvaccinated individuals and breakthrough infections in vaccinated individuals. While vaccination of unvaccinated individuals, especially in developing countries, would be more effective for reducing disease than providing a third dose to vaccinated individuals, the benefit of a third dose in reducing transmission is sizeable and increases with vaccine coverage and contact rates among individuals.

Booster vaccines protect hamsters with waning immunity from Delta VOC infection, disease, and transmission

“…Third dose boosting campaigns have therefore been initiated in many countries, with recent observational studies demonstrating a rapid increase in serum neutralizing antibody (NAb) titer and breadth against highly transmissible VOC concomitant with a decrease in infection rate and associated disease 17–26 . Modeling studies have also suggested that booster vaccination could reduce community transmission 27 . While these data are encouraging, the impact of booster vaccination after waning immunity has not been determined in a rigorously controlled experimental setting.…”

SARS-CoV-2 Transmission and Impacts of Unvaccinated-Only Screening in Populations of Mixed Vaccination Status

“…Furthermore, because precise estimates of vary by context, variant, and over time, we consider a range of values from 4 to 6. In our baseline modeling scenario, vaccines were assumed to reduce susceptibility to infection by VE S = 65%, the likelihood of transmission to others by VE I = 35%, and the likelihood of disease progression to hospitalization conditioned on infection by VE P = 86%, values which land within plausible literature estimates for the effectiveness of two doses of mRNA vaccine against the delta variant in the absence of dramatic waning and without boosting [14, 18, 21, 22]. Though less often studied in the literature, we assumed that prior SARS-CoV-2 infection would lead to 63% and 13% decreases in risk of infection and transmission based on a statistical model relating immunity to neutralization [18], and that hybrid immunity would be superior to either vaccination or prior SARS-CoV-2 infection alone.…”

“…These findings are driven by reductions in susceptibility, disease severity, and infectiousness arising from vaccination, prior SARS-CoV-2 infection, or both. However, quantitative estimates of those reductions vary depending on which vaccine was administered [17], time since vaccination or SARS-CoV-2 infection [15– 17], whether an additional “booster” dose was given [18], and the variant circulating at the time of the study [29, 30]. We therefore sought to determine how our findings might change under different sets of assumptions about vaccine effectiveness by comparing our baseline scenario (VE S = 0.65, VE I = 0.35, VE P = 0.86) with a waning/low immunity scenario (VE S = 0.5, VE I = 0.1, VE P = 0.80) and a boosted/high immunity scenario (VE S = 0.8, VE I = 0.6, VE P = 0.90), as well as a scenario reflecting plausible VE values based on early observations for the omicron variant (VE S = 0.35, VE I = 0.05, VE P = 0.77; [22, 31]).…”

“…For instance, while our analysis considered boosted, baseline, and waning scenarios for vaccines’ reductions in susceptibility VE S , infectiousness VE I , and hospitalization given infection VE P based on ranges of estimates in the current literature, few studies are available to guide estimates of similar risk reductions associated with prior SARS-CoV-2 infection, with or without vaccination (but see Refs. [14] and [18]). Moreover, real-time estimates for emerging variants of concern such as omicron require observational study and are thus unavailable for prospective policy analyses.…”

What is the vaccine effect on reducing transmission in the context of the SARS-CoV-2 delta variant?

“…The question of whether booster doses will improve the impact on transmission should be addressed as a top priority. 7 Research efforts should be directed towards enhancing existing vaccines or developing new vaccines that also protect against asymptomatic infections and onward transmission. Until we have such vaccines, public health and social measures will still need to be tailored towards mitigating community and household transmission in order to keep the pandemic at bay.…”