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NPJ Vaccines May 2024Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most...
Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.
PubMed: 38778017
DOI: 10.1038/s41541-024-00878-0 -
Vaccine May 2024The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2...
BACKGROUND
The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil.
METHODS
In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards.
RESULTS
Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history-0 (n = 26), 1 (n = 140) or 2 (n = 606) booster vaccinations-were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles.
CONCLUSIONS
Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0-2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3 months after vaccination.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT05812586.
PubMed: 38762360
DOI: 10.1016/j.vaccine.2024.05.009 -
Incidence of thrombocytopenia-associated cerebral venous sinus thrombosis: a population-based study.BMJ Neurology Open 2024The identification of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia (VITT) followed the recognition of a hitherto uncommon clinical syndrome frequently...
OBJECTIVES
The identification of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia (VITT) followed the recognition of a hitherto uncommon clinical syndrome frequently associated with cerebral venous sinus thrombosis (CVST), termed 'thrombosis with thrombocytopenia' syndrome (TTS). While anecdotally recognised as rare, the background incidence of TTS is unknown. We therefore aimed to investigate the background incidence of CVST with TTS in a large, well-defined population-based CVST cohort.
METHODS
We performed an analysis of our previously obtained retrospective population-based cohort of patients with CVST from Adelaide, Australia (2005-2011, comprising an adult population of 953 390) to identify the background incidence of CVST associated with TTS.
RESULTS
Among 105 people with CVST, the background population-based incidence of TTS-associated CVST was 1.2 per million per year (95% CI 0.5 to 2.4). A single case of a severe CVST VITT-like syndrome with multiorgan thrombosis was identified, occurring 3 weeks postrotavirus infection.
CONCLUSIONS
In our population-based study, the background incidence of CVST with associated TTS was very low, and the sole clinically severe case with multiorgan thrombosis occurred following a rotaviral precipitant. Our study establishes a benchmark against which to measure future potential 'TTS' clusters and suggests that viruses other than adenovirus may trigger this syndrome.
PubMed: 38757112
DOI: 10.1136/bmjno-2023-000605 -
Frontiers in Immunology 2024A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both...
A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.
Topics: COVID-19 Vaccines; COVID-19; SARS-CoV-2; Animals; Antibodies, Viral; Antibodies, Neutralizing; Genetic Vectors; Mice; Humans; Female; Vaccines, Synthetic; Adenoviridae; Mice, Inbred BALB C; Administration, Intranasal; Injections, Intramuscular; Immunity, Humoral; Cytokines; Immunity, Cellular
PubMed: 38745651
DOI: 10.3389/fimmu.2024.1374486 -
Lancet Regional Health. Americas Jun 2024The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second...
BACKGROUND
The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings.
METHODS
We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19.
FINDINGS
46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B.
INTERPRETATION
In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days.
FUNDING
None.
PubMed: 38737773
DOI: 10.1016/j.lana.2024.100755 -
BMC Infectious Diseases May 2024Human adenoviruses (HAdVs) have always been suggested as one of the main causes of gastroenteritis in children. However, no comprehensive report on the global... (Meta-Analysis)
Meta-Analysis
PURPOSE
Human adenoviruses (HAdVs) have always been suggested as one of the main causes of gastroenteritis in children. However, no comprehensive report on the global epidemiology of these viruses in pediatric gastroenteritis is available.
METHODS
A systematic search was conducted to obtain published papers from 2003 to 2023 in three main databases PubMed, Scopus, and Web of Science.
RESULTS
The estimated global pooled prevalence of HAdV infection in children with gastroenteritis was 10% (95% CI: 9-11%), with a growing trend after 2010. The highest prevalence was observed in Africa (20%, 95% CI: 14-26%). The prevalence was higher in inpatients (11%; 95% CI: 8-13%) and patients aged 5 years old and younger (9%; 95% CI: 7-10%). However, no significant difference was observed between male and female patients (P = 0.63). The most prevalent species was found to be the species F (57%; 95% CI: 41-72%). The most common HAdVs observed in children with gastroenteritis were types 40/41, 38, and 2. Analysis of case-control studies showed an association between HAdV and gastroenteritis in children (OR: 2.28, 95% CI; 1.51-3.44).
CONCLUSION
This study provided valuable insights into the importance of HAdVs in children with gastroenteritis, especially in hospitalized and younger children. The results can be used in future preventive measurements and the development of effective vaccines.
Topics: Humans; Gastroenteritis; Adenoviruses, Human; Adenovirus Infections, Human; Child, Preschool; Child; Infant; Prevalence; Female; Male
PubMed: 38724898
DOI: 10.1186/s12879-024-09386-x -
Journal of Infection and Public Health Jun 2024We investigated the clinical manifestation and severity of COVID-19 infection represented as a composite outcome (hospital or ICU admission, or in-hospital death) among...
BACKGROUND
We investigated the clinical manifestation and severity of COVID-19 infection represented as a composite outcome (hospital or ICU admission, or in-hospital death) among infected fully vaccinated HCWs, the RT-PCR test Ct value (Cycle Threshold) of positive fully vaccinated HCWs, and we measure the interval from the second vaccine to acquiring the infection.
METHODS
A multicenter retrospective cohort study was conducted in different regions at (16) Ministry of Defense Health Services (MODHS) hospitals. Data were restricted to fully vaccinated (minimum of 2 doses) HCWs who had a confirmed positive PCR test and employed in MODHS hospitals from August 2021 to March 2022.
RESULTS
A total of 45862 HCWs were vaccinated as of Aug 2021. Of these 1253 participants met the selection criteria and were included in the study. The average age of infected HCWs was 35.27 years (SD = ± 8.10) of which 57% were females. The HCWs were employed as doctors (24%), nurses (33%), and other (43%). The most administered vaccine type was mRNA (44%) followed by Adenovirus Viral Vector (39%) and mixed vaccine (17%). The incidence of COVID-19 vaccine breakthrough (BT) infection among HCWs was observed at 2.73% (m-RNA 3.19%, Viral Vector 2.83% and mixed 1.87%).
CONCLUSION
the overall COVID-19 (BT) infection incidence proportion was (2.73%), with the Mixed vaccine group showing the lowest (BT) incidence proportion (1.87%). The most commonly reported symptoms among (BT) infections were cough (51%), sore throat (51%), fever (47%), headache (31%), and runny nose (23%), with overall (6%) asymptomatic (BT) infections. We had (1%) hospital admissions, Zero ICU admission, and Zero deaths. our finding may indicate that infection affecting fully vaccinated patients were less severe and mostly affected the upper respiratory tract.
Topics: Humans; Female; Male; Saudi Arabia; COVID-19 Vaccines; Retrospective Studies; COVID-19; Adult; Health Personnel; SARS-CoV-2; Middle Aged; Vaccination; Hospitals; Breakthrough Infections
PubMed: 38723321
DOI: 10.1016/j.jiph.2024.04.021 -
Vaccine May 2024It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this...
It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this study was to find the optimal dose regimen for the efficacy and safety of a mixture of previously developed recombinant adenovirus-based vaccines that expressed influenza nucleoprotein, hemagglutinin, and ectodomain of matrix protein 2 (rAd/NP and rAd/HA-M2e). The vaccine efficacy and safety were measured in the immunized mice with the mixture of rAd/NP and rAd/HA-M2e intranasally or intramuscularly. The minimum dose that would be efficacious in a single intranasal administration of the vaccine mixture and cross-protective efficacy against various influenza strains were examined. In addition, the immune responses that may affect the cross-protective efficacy were measured. We found that intranasal administration is an optimal route for 10 pfu of vaccine mixture, which is effective against pre-existing immunity against adenovirus. In a study to find the minimum dose with vaccine efficacy, the 10 pfu of vaccine mixture showed higher antibody titers to the nucleoprotein than did the same dose of rAd/NP alone in the serum of immunized mice. The 10 pfu of vaccine mixture overcame the morbidity and mortality of mice against the lethal dose of pH1N1, H3N2, and H5N1 influenza infections. No noticeable side effects were observed in single and repeated toxicity studies. We found that the mucosal administration of adenovirus-based universal influenza vaccine has both efficacy and safety, and can provide cross-protection against various influenza infections even at doses lower than those previously known to be effective.
Topics: Animals; Influenza Vaccines; Viral Matrix Proteins; Adenoviridae; Administration, Intranasal; Hemagglutinin Glycoproteins, Influenza Virus; Mice; Cross Protection; Antibodies, Viral; Orthomyxoviridae Infections; Female; Mice, Inbred BALB C; Influenza A Virus, H3N2 Subtype; Vaccines, Synthetic; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Vaccine Efficacy; Nucleoproteins; Viral Core Proteins; Injections, Intramuscular; Viroporin Proteins
PubMed: 38714444
DOI: 10.1016/j.vaccine.2024.04.054 -
Journal of Primary Care & Community... 2024In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders...
In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.
Topics: Adult; Female; Humans; Male; Middle Aged; COVID-19; COVID-19 Vaccines; Immunization, Secondary; Iran; SARS-CoV-2; Vaccination; Post-Acute COVID-19 Syndrome
PubMed: 38708693
DOI: 10.1177/21501319241251941 -
MedComm May 2024Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants,...
Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5-Beta/Deta vaccine induced robust broad-spectrum neutralization against Omicron BA.5-included variants. IN immunization with Ad5-Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue-resident memory T cells (T) in respiratory tract. The combination of IM and IN delivery of the Ad5-Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5-Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5-Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS-CoV-2 pre-Omicron variants of concern and BA.5-included Omicron subvariants.
PubMed: 38680520
DOI: 10.1002/mco2.539