Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report

Abstract

Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x1010 virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada

“…In immunogenicity studies, heterologous ChAdOx1 followed by mRNA vaccination induced antibody titers exceeding homologous vector vaccination and comparable to homologous mRNA vaccination. [11][12][13] For pragmatic and immunologic reasons, some countries (e.g. France, Germany, Spain, the United Kingdom (UK)) have, like Canada, recommended and accepted mixed schedules as providing valid two-dose protection.…”

Predicted Symptomatic Effectiveness of Pfizer-BioNTech BNT162b2 Vaccine Against Omicron Variant of SARS-CoV-2

“…Protection after the third dose would be substantially stronger across all the scenarios considered, given the likely neutralisation increase relative to the second dose. In fact, the assumed 3.3-fold increase could be too conservative, given the 20x (15, 27) increase reported in Atmar et al [2021] for homological Comirnaty boosting, and the 25x increase from the early data in Pfizer/BioNTech [2021] on Omicron pseudovirus neutralisation. The symptomatic effectiveness, predicted here for general adult populations, is likely to be higher in adolescents and young adults.…”

Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

“…Other studies have assessed the safety and immunogenicity of heterologous prime-boost regimens involving different vaccine platforms. A recent study involving individuals who originally received one of the three EUA vaccines (mRNA-1273, Ad26.COV2.S, or BNT162b2) and were subsequently boosted with a homologous or heterologous vaccine suggests that both boosting schedules increase protective efficacy against symptomatic SARS-CoV-2 infection [39]. In a separate study, favorable increases in humoral responses were observed in individuals previously vaccinated with the ChAdOx1 nCoV-19 vaccine and subsequently boosted with BNT162b2 [40, 41].…”