Project description:To enhance the personal immunity to COVID-19, a third booster dose of inactivated COVID-19 vaccines program campaign was implemented in China. Our study endeavored to compare the dynamics of neutralizing antibodies generated by four distinct booster vaccines against three kinds of live SARS-CoV-2 virus (wild-type, Delta AY.23, and Omicron BA5.2). This cohort study involved 320 healthy individuals, who were randomly assigned to four groups, to receive boosters with inactivated vaccine (COVac and BIBP), the adenovirus type-5-vectored vaccine (Convidecia), and the recombinant protein-based vaccine (Zifivax), respectively, all the vaccines studied had the Wuhan variant as their parental variant. Participants were recruited from December 2021 to June 2022, with a follow-up period of 180 days. We evaluated humoral immune responses and their longevity by measuring the geometric mean titers (GMTs) of neutralizing antibodies against the SARS-CoV-2 virus at various time points post-boost. After 180 days of follow-up, 310 participants completed the study. Across all booster groups, neutralizing antibodies against the wild-type virus declined sharply within the first 90 days, accounting for an 81.24 to 92.34% reduction, then slowed down with gradually decreasing decay rates. By day 14 of post-boost, the ability to neutralize the Delta variant slightly diminished compared to the wild-type, whereas neutralizing antibodies against the Omicron variant exhibited a more pronounced decline, ranging from 10.78 to 19.88 times lower than those against the wild-type. Notably, heterologous boosting with the Convidecia vaccine maintained higher GMTs of neutralizing antibodies against both Delta and Omicron variants compared to the other boosters. At 180 days of post-boost, GMTs of neutralizing antibodies against SARS-CoV-2 had substantially decreased, yet individuals who received the Convidecia vaccine still exhibited higher titers than those who received other boosters. In summary, neutralizing antibody levels significantly waned 180 days after the third vaccine dose, with the most pronounced decline occurring within the initial 90 days. Heterologous boosting with Convidecia demonstrated a more robust, durable, and broad humoral immune response compared to boosting with inactivated vaccines or Zifivax, suggesting that adenovirus vector vaccines possess a special advantage in the realm of vaccine development for preventing infectious diseases.

Project description:ImportanceAntibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting.ObjectiveTo evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2.Design, setting, and participantsIn this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022.ExposuresParticipants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2.Main outcomes and measuresHumoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8+ and CD4+ T-cell responses were evaluated by intracellular cytokine staining assays.ResultsAmong 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16.Conclusions and relevanceHeterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.

Project description:ImportanceAssessing booster effectiveness of COVID-19 mRNA vaccine and inactivated SARS-CoV-2 vaccine over longer time intervals and in response to any further SARS-CoV-2 variants is crucial in determining optimal COVID-19 vaccination strategies.ObjectiveTo determine levels of protection against severe COVID-19 and confirmed SARS-CoV-2 infection by types and combinations of vaccine boosters in Singapore during the Omicron wave.Design, setting, and participantsThis cohort study included Singapore residents aged 30 years or more vaccinated with either at least 2 doses of mRNA COVID-19 vaccines (ie, Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or inactivated SARS-CoV-2 vaccines (Sinovac CoronaVac or Sinopharm BBIBP-CorV) as of March 10, 2022. Individuals with a known SARS-CoV-2 infection prior to December 27, 2021, an infection on or before the date of their second vaccine dose, or with reinfection cases were excluded.ExposuresTwo or 3 doses of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Sinovac CoronaVac, or Sinopharm BBIBP-CorV.Main outcomes and measuresNotified infections from December 27, 2021, to March 10, 2022, adjusted for age, sex, race, housing status, and calendar days. Estimated booster effectiveness, defined as the relative incidence-rate reduction of severe disease (supplemental oxygen, intensive care, or death) or confirmed infection following 3-dose vaccination compared with 5 months after second mRNA dose, was determined using binomial regression.ResultsAmong 2 441 581 eligible individuals (1 279 047 [52.4%] women, 846 110 (34.7%) aged 60 years and older), there were 319 943 (13.1%) confirmed SARS-CoV-2 infections, of which 1513 (0.4%) were severe COVID-19 cases. mRNA booster effectiveness against confirmed infection 15 to 60 days after boosting was estimated to range from 31.7% to 41.3% for the 4 boosting combinations (homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and 2-dose mRNA-1273/BNT162b2 booster). Five months and more after boosting, estimated booster effectiveness against confirmed infection waned, ranging from -2.8% to 14.6%. Against severe COVID-19, estimated mRNA booster effectiveness was 87.4% (95% CI, 83.3%-90.5%) 15 to 60 days after boosting and 87.2% (95% CI, 84.2%-89.7%) 5 to 6 months after boosting, with no significant difference comparing vaccine combinations. Booster effectiveness against severe COVID-19 15 days to 330 days after 3-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6% (95% CI, 48.7%-81.9%).Conclusions and relevanceBooster mRNA vaccine protection against severe COVID-19 was estimated to be durable over 6 months. Three-dose inactivated SARS-CoV-2 vaccination provided greater protection than 2-dose but weaker protection compared with 3-dose mRNA.

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:BackgroundAlthough 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.MethodsIn 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.ResultsOf 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.ConclusionsHomologous 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.).

Project description:ObjectiveTo evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital admission, and death.DesignLiving systematic review and network meta-analysis.Data sourcesWorld Health Organization covid-19 databases, including 38 sources of published studies and preprints.Study selectionRandomised controlled trials, cohort studies, and case-control studies.Methods38 WHO covid-19 databases were searched on a weekly basis from 8 March 2022 to 31 July 2022. Studies that assessed the effectiveness of heterologous and homologous covid-19 vaccine regimens with or without a booster were identified. Studies were eligible when they reported the number of documented, symptomatic, severe covid-19 infections, covid-19 related hospital admissions, or covid-19 related deaths among populations that were vaccinated and unvaccinated. The primary measure was vaccine effectiveness calculated as 1−odds ratio. Secondary measures were surface under the cumulative ranking curve (SUCRA) scores and the relative effects for pairwise comparisons. The risk of bias was evaluated by using the risk of bias in non-randomised studies of interventions (ROBINS-I) tool for all cohort and case-control studies. The Cochrane risk of bias tool (version 2; ROB-2) was used to assess randomised controlled trials.ResultsThe second iteration of the analysis comprised 63 studies. 25 combinations of covid-19 vaccine regimens were identified, of which three doses of mRNA vaccine were found to be 93% (95% credible interval 70% to 98%) effective against asymptomatic or symptomatic covid-19 infections for non-delta or non-omicron related infections. Heterologous boosting using two dose adenovirus vector vaccines with one dose mRNA vaccine showed a vaccine effectiveness of 94% (72% to 99%) against non-delta or non-omicron related asymptomatic or symptomatic infections. Three doses of mRNA vaccine were found to be the most effective in reducing non-delta or non-omicron related hospital admission (96%, 82% to 99%). The vaccine effectiveness against death in people who received three doses of mRNA vaccine remains uncertain owing to confounders. The estimate for a four dose mRNA vaccine regimen was of low certainty, as only one study on the effectiveness of four doses could be included in this update. More evidence on four dose regimens will be needed to accurately assess the effectiveness of a fourth vaccine dose. For people with delta or omicron related infection, a two dose regimen of an adenovirus vector vaccine with one dose of mRNA booster was 77% (42% to 91%) effective against asymptomatic or symptomatic covid-19 infections, and a three dose regimen of a mRNA vaccine was 93% (76% to 98%) effective against covid-19 related hospital admission.ConclusionAn mRNA booster is recommended to supplement any primary vaccine course. Heterologous and homologous three dose regimens work comparably well in preventing covid-19 infections, even against different variants. The effectiveness of three dose vaccine regimens against covid-19 related death remains uncertain.Systematic review registrationThis review was not registered. The protocol is included in the supplementary document.Readers' noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 31 May 2022 (BMJ 2022;377:e069989), and previous versions can be found as data supplements (https://www.bmj.com/content/377/bmj-2022-069989/related). When citing this paper please consider adding the version number and date of access for clarity.

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Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore.

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Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore.

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