Dataset Information

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 5×10¹⁰ 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.).

SUBMITTER: Atmar RL

PROVIDER: S-EPMC8820244 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Homologous and Heterologous Covid-19 Booster Vaccinations.

Atmar Robert L RL Lyke Kirsten E KE Deming Meagan E ME Jackson Lisa A LA Branche Angela R AR El Sahly Hana M HM Rostad Christina A CA Martin Judith M JM Johnston Christine C Rupp Richard E RE Mulligan Mark J MJ Brady Rebecca C RC Frenck Robert W RW Bäcker Martín M Kottkamp Angelica C AC Babu Tara M TM Rajakumar Kumaravel K Edupuganti Srilatha S Dobrzynski David D Coler Rhea N RN Posavad Christine M CM Archer Janet I JI Crandon Sonja S Nayak Seema U SU Szydlo Daniel D Zemanek Jillian A JA Dominguez Islas Clara P CP Brown Elizabeth R ER Suthar Mehul S MS McElrath M Juliana MJ McDermott Adrian B AB O'Connell Sarah E SE Montefiori David C DC Eaton Amanda A Neuzil Kathleen M KM Stephens David S DS Roberts Paul C PC Beigel John H JH

The New England journal of medicine 20220126 11

<h4>Background</h4>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.<h4>Methods</h4>In this phase 1-2, open-label clinical trial conducted at 10 sites in the United St ...[more]

PMID: 35081293

Similar Datasets

Project description:BackgroundBooster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied.MethodsWe conducted a non-randomized, non-blinded phase II observational community trial acrossBahrain, investigating the reactogenic and immunogenic responseof participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological statuswas determined at baseline and on the following 8thweek. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling.Results305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study,with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred.ConclusionHeterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated. Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.

Project description:BackgroundHeterologous booster vaccines are more effective than homologous booster vaccines in combating the coronavirus disease 2019 (COVID-19) outbreak. However, our understanding of homologous and heterologous booster vaccines for COVID-19 remains limited.MethodsWe recruited 34 healthy participants from two cohorts who were primed with two-dose inactivated COVID-19 vaccine before, vaccinated with COVID-19 inactivated vaccine and adenovirus-vectored vaccine (intramuscular and aerosol inhalation of Ad5-nCoV) as a third booster dose. We assessed the immune responses of participants before and 14 days after vaccination, including levels of neutralizing antibodies, IgG, and cytokines, and quantified the transcriptional profile of peripheral blood mononuclear cells (PBMCs).ResultsThe Ad5-nCoV group showed a significantly higher neutralizing antibody geometric mean titer (GMT) compared to the ICV group after 14 days of heterologous boosting. The intramuscular Ad5-nCoV group had a GMT of 191.8 (95% CI 129.0, 285.1) compared to 38.1 (95% CI 23.1, 62.8) in the ICV1 group (p<0.0001). The aerosolized Ad5-nCoV group had a GMT of 738.4 (95% CI 250.9-2173.0) compared to 244.0 (95% CI 135.0, 441.2) in the ICV2 group (p=0.0434). Participants in the aerosolized Ad5-nCoV group had median IFN-γ+ spot counts of 36.5 (IQR 15.3-58.8) per 106 PBMCs, whereas, both intramuscular Ad5-nCoV and CoronaVac immunization as the third dose showed lower responses. This suggests that a third dose of booster Ad5-nCoV vaccine (especially aerosolized inhalation) as a heterologous vaccine booster induces stronger humoral and cellular immune responses, which may be more potent against VOCs than the use of inactivated vaccine homologs. In transcriptomic analyses, both aerosolized inhalation/intramuscular injection of the Ad5-nCoV vaccine and inactivated vaccine induced a large number of differentially expressed genes that were significantly associated with several important innate immune pathways including inflammatory responses, regulation of the defense response, and regulation of cytokine production. In addition, we identified crucial molecular modules of protective immunity that are significantly correlated with vaccine type and neutralizing antibodies level.ConclusionThis study demonstrated that inhalation/intramuscular injection of the Ad5-nCoV vaccine-mediated stronger humoral and cellular immune responses compared with the inactivated vaccine, and correlated significantly with innate immune function modules, supporting a heterologous booster immunization strategy.

Dataset Information

Homologous and Heterologous Covid-19 Booster Vaccinations.

Background

Methods

Results

Conclusions

Publications

Homologous and Heterologous Covid-19 Booster Vaccinations.

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