The anticipated 80% seroresponse rate was based on previously observed responses to homologous and heterologous booster doses in CoronaVac-primed Brazilian adults measured in the same laboratory as in the present study.8 In that study, done in August 2021 prior to the most recent two waves of COVID-19 in Brazil in January and June 2022,17 the participants had low antibody concentrations at baseline with anti-spike IgG GMCs ranging from 3745 to 4433 AU/mL across the four study groups. responses as were Eicosadienoic acid pseudo-neutralizing responses against SARS-CoV-2 prototype and Omicron BA.4/5 variants. All vaccinations were well tolerated with no vaccine-related serious adverse events and mainly transient mild-to-moderate local and systemic reactogenicity. Heterologous boosting with full or half doses of ChAdOx1-S or a half dose of BNT162b2 was safe and immunogenic in CoronaVac-primed adults, but seroresponse rates were limited by high baseline immunity. KEYWORDS: COVID-19, vaccine, heterologous booster, fractional dose, neutralizing antibodies, ChAdOx1-S, BNT162b2 Introduction Although the numbers of cases of COVID-19 appeared to be declining steadily since 2021, new waves of infection due to Eicosadienoic acid Omicron variants in 2022 illustrated the potential threat of new outbreaks due to the emergence of new variants of SARS-CoV-2.1 To move COVID-19 from a pandemic to an endemic disease, the global population has to have substantial protective immunity following extensive immunization campaigns and from widespread infection, giving hybrid immunity against the newest strains FASLG to emerge. However, while immunity to severe lower respiratory tract COVID-19 remains high, immunity to illness in the top respiratory tract with successive growing variants of the virus is limited as a result of a combination of waning antibodies,2 and lower effectiveness of postinfection immunity and the original vaccines against the new variants.3 The second option is due to the successive build up of mutations in the spike protein (S-protein) of the new variants which is the main antigenic target of most vaccines.4 This results Eicosadienoic acid in the original vaccines being less effective at avoiding infection due to immune evasion by the new variants,5 putting at risk frail individuals or those Eicosadienoic acid with significant comorbidities, just as with other respiratory viral infections in these cohorts. Ideally, fresh vaccines would be developed that match current and future variants, but as it is not possible to forecast the next variant it is necessary to maintain a high level of immunity among the vulnerable. Current vaccines should be used to boost vaccine-induced immunity, while at the same time attempting to broaden the antibody response to minimize the effect of vaccine evasion by growing variants. Heterologous booster vaccination offers been shown to be effective in increasing vaccine-derived immunity as well as increasing the breadth of the reactions against fresh variants.6C10 However, booster vaccination campaigns may be hampered by restricted availability and cost of COVID-19 vaccines leading to inequitable distribution of the global supply resulting in low coverage rates in many regions, including Southeast Asia11 and Africa.12 Similar issues of restricted supply of additional vaccines, particularly those widely used in low- and middle-income countries, have resulted in the use of fractional doses of those vaccines as booster doses; examples include inactivated poliovirus vaccine (IPV),13 yellow fever vaccine14 and malaria vaccine.15 The present study was performed to assess the potential of two different COVID-19 vaccines, ChAdOx1-S and BNT162b2, as heterologous boosters in the Brazilian adult population following priming by two primary doses of the whole-virus inactivated COVID-19 vaccine, CoronaVac. This included the use of half doses to explore the potential of a fractional dose strategy to increase protection with COVID-19 vaccines as heterologous booster doses in previously primed individuals. Methods This phase.