Homologous and Heterologous Covid-19 Booster Vaccinations

Abstract

Background Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. Methods In this phase 1–2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson–Janssen) at a dose of 5×10 10 virus particles, or BNT162b2 (Pfizer–BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. Results Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. Conclusions Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209 .)

Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination

“…Immunogenicity following heterologous boosting (3rd dose) with mRNA vaccines compared to homologous mRNA vaccines have been reported recently. 14 In a large, open-label clinical trial, 458 adult participants who had completed two doses of COVID-19 vaccine regimen at least 12 weeks earlier, received a booster with one of three vaccines included mRNA-1273, Ad26.COV2.S (Johnson & Johnson-Janssen), or BNT-162b2 at least 12 weeks apart. They found a similar increased trends of geometric mean binding antibody titers among participants who had received homologous or heterologous prime-booster mRNA vaccines.…”

Effectiveness of Homologous or Heterologous Covid-19 Boosters in Veterans

“…Recent clinical trials examining the safety and immunogenicity of SARS-CoV-2 boosters in healthy adults have shown greater increases in antibody titers after heterologous boosting than after homologous boosting. 2 , 5 In particular, neutralizing immunoglobulin G antibodies were lowest after homologous Ad26.COV2.S boosting and remained below the predicted efficacy threshold for preventing symptomatic Covid-19. 2 …”

“… 2 , 5 In particular, neutralizing immunoglobulin G antibodies were lowest after homologous Ad26.COV2.S boosting and remained below the predicted efficacy threshold for preventing symptomatic Covid-19. 2 …”

“…1 Clinical trials have shown that receipt of a booster that does not match the primary vaccination (heterologous booster) may result in a higher neutralizing-antibody response than the receipt of a matching (homologous) booster, particularly after primary vaccination with an adenoviral-vector vaccine. 2-5 Whether the choice of booster affects real-world vaccine effectiveness is poorly understood.…”

COVID-19 immunisation in older people

“…Indeed, the continued emergence of viral variants causing de novo or breakthrough infections raises new concerns for the swift implementation of COVID-19 vaccination. Recent evidence supports the need for a booster dose 5 to prevent SARS-CoV-2 infection with the B.1.1.529 (omicron) variant, with the effectiveness of three doses ranging from 55% to 80%, compared to 0–20% protection with two doses. 6 Therefore, avoiding the insurgence of new variants and stopping the unconstrained spread of SARS-CoV-2 via extensive vaccination coverage is crucial for the potential evolution of COVID-19 into an endemic disease.…”