Table 1.
Summary of included studies on heterologous COVID-19 vaccination.
| Study | Regimen (Prime-Boost) | Country | Design | Participants (N) | Age (Years) | Common Side Effects (%) | Severe Adverse Events | Interval Boost Duration | Cellular Immune Response | Humoral Immune Response | Outcome | Funding | Declaration of Interests |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Logunov et al. (NCT04436471, NCT04437875) [34] | Sputnik V (rAd26 and rAd5) | Russia | Open, non-randomised phase 1/2 | 76 healthy adults(23 women and 53 men) | 18–60 | Pain at injection site (58%), hyperthermia (50%), headache (42%), asthenia (28%), muscle and joint pain (24%) | None | 21 days | All participants, with median cell proliferation of 2.5% CD4+ and 1.3% CD8+ | All participants produced antibodies to SARS-CoV-2 glycoprotein (100% seroconversion) | Good safety profile and induced strong humoral–cellular immune responses | Ministry of Health of the Russian Federation | Yes |
| Logunov et al. (NCT04530396) [35] | Sputnik V | Russia (Multicenter) | Randomised, double-blind, placebo-controlled, phase 3 trial | 21,977 healthy adults (vaccine group: 14,964 **—5821 women and 9143 men; placebo group: 4902 **—1887 women and 3015 men) | ≥18 | Flu-like illness, injection site reactions, headache, and asthenia | 68 participants (45- vaccine group, 23 placebo group) * | 21 days | All participants in the vaccine group had significantly higher levels of IFN-γ | 98·25% seroconversion (four-fold increase in titre at 42 days compared with the day before first vaccination) in the vaccine group (participants produced antibodies to SARS-CoV-2 glycoprotein) | Good safety profile and induced strong humoral–cellular immune responses.May also induce broad antibody response with ability to recognize wide variety of epitopes on SARS-CoV-2 glycoprotein S | Moscow City Health Department, Russian Direct Investment Fund, and Sberbank | Yes |
| Liu et al. (ISRCTN, 69254139) [12] | ChAd and BNT | UK (Multicenter) | Randomised, non-inferiority trial | 830 (adults with no or well controlled comorbidities) (463 prime-boost regimen—212 women, and 251 men) | >50 | Both heterologous schedules (at 28- and 84-day prime-boost intervals) induced greater systemic and local reactogenicity than their homologous counterparts | 4 * | 28-day (463 participants) and 84-day (367 participants) | NA | NA | These data support flexibility in use of heterologous prime-boost vaccination (using ChAd and BNT COVID-19 vaccines) | UK Vaccine Task Force and National Institute for Health Research | Yes |
| Borobia et al. (NCT04860739) [10] |
ChAd (prime) and BNT (booster) | Spain (Multicenter) | Phase 2, open label, randomised, controlled trial | 676(382 women and 294 men) | 18–60 | Injection site pain (88%), induration (35%), headache (44%), and myalgia (43%) | None | 8–12 weeks (61%: 8–9 weeks; 39%: 10–12 weeks) | All participants in the vaccine group had significantly higher levels of IFN-γ | All participants produced in the vaccine group produced antibodies to SARS-CoV-2 glycoprotein (100% seroconversion; >0.8 BAU/mL) | Induced strong humoral–cellular immune responses, with an acceptable and manageable reactogenicity profile | Instituto de Salud Carlos III | Yes |
| Atmar et al. (NCT04889209) [36] | mRNA-1273, ChAd, and BNT | US (Multicenter) | Open, non-randomised phase 1/2 | 458 healthy adults (231 women and 227 men) (Booster-154 mRNA-1273, 150 ChAd, and 153 BNT) | ≥18 | Site pain, malaise, headache, and myalgiaSimilar reactogenicity profile between the groups | NA | 21–28 days | Stimulated an anamnestic response in persons who previously received primary series of any of these vaccines | Heterologous regimens increased antibody titers by 6.2–76-times, compared to the 4.2–20-times increase after homologous regimen | NIH, CIVICs | None | |
rAd = recombinant adenoviruses vectors; CD = cluster of differentiation; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; BNT = BNT162b2 vaccine, Pfizer–BioNTech; ChAd = ChAdOx1 nCoV-19 vaccine, AstraZeneca; IFN-γ = interferon gamma; BAU = binding antibody units; * = serious adverse events were considered not to be related to vaccination; ** = participants included in primary outcome analysis; NIH = National Institute of Health; NIAID = National Institute for Allergy and Infectious Diseases; CIVICs = NIAID Collaborative Influenza Vaccine Innovation Centers.