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Background: In response to the coronavirus disease 2019 (Covid-19) pandemic, Brazil authorised the Astra Zeneca/Fiocruz vaccine in January 2021. As the Delta variant emerged in May 2021, interval between vaccine doses was adjusted. By September 2021, the Brazilian National Immunisation Program recommended a booster dose for individuals over 70, and later expanded the recommendation to all adults., Objectives: Assess the equivalence of IgG antibody response against the Covid-19 S protein before and approximately 28 days after the third dose of a Covid-19 recombinant vaccine. Two groups received initial two doses with intervals of eight and 12 weeks., Methods: This is a phase IV clinical study, uncontrolled, non-randomised. The study proposes calculating the ratio of geometric means titres (GMT) 28 days after the third dose, with a target ratio of confidence interval (CI) between 0.77 and 1.3., Findings: In the primary endpoint, there was no equivalence between the eight- and 12-week intervals with a slight variation favouring the eight-week group. Post-third dose, both groups showed increases titres at 28 days, three months, six months and 12 months. Both groups responded similarly to Delta and Omicron BA.1, with a more significant increase for Delta., Main Conclusions: The study showed strong and consistent immune response in all age groups receiving the Covid-19 recombinant vaccine. Third dose elicited an increase in GMT by at least three times aligned with Ministry of Health strategies emphasising Bio-Manguinhos crucial role in pandemic control in the country.

Background: The emergence of new variants of SARS-CoV-2 has led to the administration of different booster vaccines to mitigate COVID-19. Vaccines with adenoviral vectors have been rarely associated with vaccine-induced immune thrombotic thrombocytopenia (VITT)., Objectives: This study aimed to describe 15 cases of VITT after the third and fourth doses of the COVID-19 vaccine in Brazil., Methods: Cases were reported after all kinds of anti-SARS-CoV-2 booster vaccinations between October 17, 2021, and September 4, 2022., Results: Of the 26 suspected cases, 15 cases of VITT were analyzed. Of these, 10 were classified as definite VITT, 2 as probable, 1 as possible, and 2 as unlikely. The estimated frequency of definite, probable, or possible VITT was 0.33 cases per million. Cases were assigned to ChAdOx1 (13 cases), Ad26.COV2.S (1 case), and BNT162b2 (1 case). None of the patients received an adenoviral vaccine as a primary vaccination. The average age of participants was 34 years, and symptoms usually appeared 8 days after vaccination. Headache was the most common symptom, and cerebral veins were the most affected thrombotic site. The overall mortality risk was 53%. Anti-platelet factor 4 enzyme-linked immunosorbent assay serology was positive in 11 out of 15 patients (73.3%), negative in 2 (13.3%), and missing in 2 (13.3%)., Conclusion: The study confirms that VITT is linked to the first exposure to adenoviral vector vaccines. Since January 2023, Brazil has recommended preferably COVID-19 messenger RNA vaccines for individuals aged 18 to 39 years. We suggest that, in the current disease scenario, COVID-19 adenovirus vaccines should not be the first choice for individuals aged <50 years who have not received a previous dose of this type of vaccine., (© 2023 The Author(s).)

The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9 Mths -4 Yrs and 288 adults/18-49 Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9 Mths -2 Yrs ). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9 Mths -2 Yrs ) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9 Mths -2 Yrs ). Biomarker signatures further support that only Younger Children (9 Mths -2 Yrs ) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The present study aims to determine whether 17DD-YF-specific humoral and cellular immunological memory is maintained 8-years after primary vaccination with subdoses (10,447IU;3,013IU;587IU;158IU;31IU). For this purpose, this follow-up study was carried out in a subset of volunteers ( n = 98) originally enrolled in the dose-response study in 2009 and 46 non-vaccinated controls. Our results demonstrated that vaccinees, who had seroconverted following primary vaccination and had not been revaccinated, present similar neutralizing antibodies levels and YF-specific cellular memory, particularly CMCD4 and EMCD8 as compared to the reference full dose (27,476IU). Although, PRNT seropositivity rates were similar across subgroups (94, 82, 83, 94, 80, and 91%, correspondingly), only doses above 587IU elicited similar iterative proportion of seropositivity rates, calculated as a progressive decrease on seropositivity rates along time (89, 80, 80, and 91%, respectively) as compared to 158IU and 31IU (68 and 46%, respectively). Noteworthy were the strong positive correlations ("EMCD4,EMCD8" and "TNFCD8,IFNCD8") observed in most subdoses, except for 31IU. Major similarities underscored the preserved antibody titers and the outstanding levels of EMCD8, relevant correlates of protection for YF-specific immunity. These findings provide evidences to support the regular use of dose sparing strategy for YF vaccine in adults.