Project description:BackgroundThe objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies.MethodsPubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted.ResultsNineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant.ConclusionsThe current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.
Project description:Adults receiving heterologous COVID-19 immunisation with mRNA (Comirnaty) or adenoviral-vector (Vaxzevria) vaccines had higher reactogenicity rates and sought medical attention more often after two doses than homologous schedules. Reactogenicity was higher among ≤ 50 than > 50 year-olds, women and those with prior symptomatic/confirmed COVID-19. Adults receiving heterologous schedules on clinical advice after severe first-dose reactions had lower reactogenicity after dose 2 following Vaxzevria/Comirnaty (93.4%; 95% confidence interval: 90.5-98.1 vs 48% (41.0-57.7) but not Comirnaty/Vaxzevria (91.7%; (77.5-98.2 vs 75.0% (57.8-87.9).
Project description:During spring 2021, AZD1222 and BNT162b2 were used as prime and BNT162b2 as booster COVID-19 vaccines in Denmark. We obtained self-reported information on systemic reactogenicity day-by-day during two weeks for 2862 healthcare workers vaccinated with heterologous AZD1222 + BNT162b2 or homologous BNT162b2 + BNT162b2 regimens and compared prevalences of symptoms with unvaccinated healthcare workers. We found comparable systemic reactogenicity during the first week in the two vaccine regimens and no reactogenicity during the second week. Most of the symptoms returned to a level equal to the control population four days after booster vaccination.
Project description:Background/objectiveHeterologous prime-boost doses of COVID-19 vaccines ('mix-and-match' approach) are being studied to test for the effectiveness of Oxford (AZD1222), Pfizer (BNT162b2), Moderna (mRNA-1273) and Novavax (NVX-CoV2373) vaccines for COVID in 'Com-Cov2 trial' in UK, and that of Oxford and Pfizer vaccines in 'CombivacS trial' in Spain. Later, other heterologous combinations of CoronaVac (DB15806), Janssen (JNJ-78436735), CanSino (AD5-nCOV) and other were also being trialled to explore their effectiveness. Previously, such a strategy was deployed for HIV, Ebola virus, malaria, tuberculosis, influenza and hepatitis B to develop the artificial acquired active immunity. The present review explores the science behind such an approach for candidate COVID-19 vaccines developed using 11 different platforms approved by the World Health Organization.MethodsThe candidate vaccines' pharmaceutical parameters (e.g. platforms, number needed to vaccinate and intervals, adjuvanted status, excipients and preservatives added, efficacy and effectiveness, vaccine adverse events, and boosters), and clinical aspects must be analysed for the mix-and-match approach. Results prime-boost trials showed safety, effectiveness, higher systemic reactogenicity, well tolerability with improved immunogenicity, and flexibility profiles for future vaccinations, especially during acute and global shortages, compared to the homologous counterparts.ConclusionStill, large controlled trials are warranted to address challenging variants of concerns including Omicron and other, and to generalize the effectiveness of the approach in regular as well as emergency use during vaccine scarcity.
Project description:IntroductionCoronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime-boost vaccination with different vaccines remain largely unclear.Areas coveredElectronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination.As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2).Expert opinionOur systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals.
Project description:Three commercial vaccines are administered in domestic livestock farms for routine vaccination to aid for foot-and-mouth disease (FMD) control in Korea. Each vaccine contains distinct combinations of inactivated serotype O and A FMD virus (FMDV) antigens: O/Manisa + O/3039 + A/Iraq formulated in a double oil emulsion (DOE), O/Primorsky + A/Zabaikalsky formulated in a DOE, and O/Campos + A/Cruzeiro + A/2001 formulated in a single oil emulsion. Despite the recommendation for a prime-boost vaccination with the same vaccine in fattening pigs, occasional cross-inoculation is inevitable for many reasons, such as lack of compliance with vaccination guidelines, erroneous application, or change in vaccine types by suppliers. Therefore, there have been concerns that a poor immune response could be induced by cross-inoculation due to a failure to boost the immune response. In the present study, it was demonstrated by virus neutralization and ELISA tests that cross-inoculation of pigs with three commercial FMD vaccines does not hamper the immune response against the primary vaccine strains and enhances broader cross-reactivity against heterologous vaccine antigens whether they were applied or not. Therefore, it could be concluded that the cross-inoculation of FMD vaccines can be used as a regimen to strategically overcome the limitation of the antigenic spectrum induced by the original regimen.
Project description:The Epstein-Barr virus (EBV) is one of the predominant tumor viruses in humans, but so far no therapeutic or prophylactic vaccination against this transforming pathogen is available. We demonstrated that heterologous prime-boost vaccination with the nuclear antigen 1 of EBV (EBNA1), either targeted to the DEC205 receptor on DCs or expressed from a recombinant modified vaccinia virus Ankara (MVA) vector, improved priming of antigen-specific CD4+ T cell help. This help supported the expansion and maintenance of EBNA1-specific CD8+ T cells that are most efficiently primed by recombinant adenoviruses that encode EBNA1. These combined CD4+ and CD8+ T cell responses protected against EBNA1-expressing T and B cell lymphomas, including lymphoproliferations that emerged spontaneously after EBNA1 expression. In particular, the heterologous EBNA1-expressing adenovirus, boosted by EBNA1-encoding MVA vaccination, demonstrated protection as a prophylactic and therapeutic treatment for the respective lymphoma challenges. Our study shows that such heterologous prime-boost vaccinations against EBV-associated malignancies as well as symptomatic primary EBV infection should be further explored for clinical development.
Project description:BackgroundThe effectiveness of heterologous prime-boost Coronavirus disease 2019 (Covid-19) vaccination is currently unknown.MethodsFrom individuals vaccinated with two doses against Covid-19 in Sweden until July 5, 2021 (N=3,445,061), we formed a study cohort including 94,569 individuals that had received heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, 16,402 individuals that received heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination, and 430,100 individuals that received homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 prime-boost vaccination. In addition, 180,716 individuals were selected who were unvaccinated at the date of vaccination in the corresponding case. Unvaccinated individuals were censored at first dose of any vaccine. Baseline was the date of the second dose of any vaccine, with the same date in the corresponding unvaccinated individual. The outcome included incident symptomatic Covid-19 infection occurring >14 days after baseline.FindingsDuring a mean follow-up time of 76 (range 1-183) days, symptomatic Covid-19 infection was confirmed in 187 individuals with heterologous vaccine schedules (incidence rate: 2.0/100,000 person-days) and in 306 individuals from the unvaccinated control group (incidence rate: 7.1/100,000 person-days). The adjusted vaccine effectiveness was 67% (95% CI, 59-73, P<0.001) for heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, and 79% (95% CI, 62-88, P<0.001) for heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination. When combined and analysed together, the two heterologous vaccine schedules had an effectiveness of 68% (95% CI, 61-74, P<0.001) which was significantly greater (Pinteraction<0.001) than the 50% effectiveness for homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 (95% CI, 41-58, P<0.001).InterpretationThe findings of this study suggest that the use of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination is an effective alternative to increase population immunity against Covid-19, including against the Delta variant which dominated the confirmed cases during the study period. These findings could have important implications for vaccination strategies and logistics, and consequently in the battle against the Covid-19 pandemic.