Our study is also limited by the relatively small number of samples considering the large heterogenicity of the study subject. past contamination, and period from last vaccination. Our data suggest that COVID19 vaccines are highly effective in inducing protective humoral immunity. This effectiveness, however, is potentially reduced among obese individuals which spotlight the importance of booster doses to Zfp264 improve their neutralizing immunity. Further investigations on larger sample size remain necessary to comprehensively conclude about the effect of obesity on COVID19 vaccine effectiveness on humoral immunity induction. Keywords:COVID19 vaccine, ELISA, humoral immunity, mRNA vaccine, obesity, SARSCoV2 == 1. INTRODUCTION == Obesity is the leading metabolic disease in the 21st Century.1It is now recognized as a worldwide pandemic affecting both genders of all age groups.2,3Increased morbidity and mortality are associated with obesity and its related impaired metabolic health complications such as insulin resistance, diabetes mellitus, hyperlipidemia, hypercholesterolemia, endothelial dysfunction, and cardiovascular disorders.4Individuals with obesity confers a state of lowgrade inflammation as evidenced by increased peripheral white leukocyte count, and induction of cytokine and chemokine secretion.5The primary site of this inflammatory response is adipose tissues, but its effects can extend to other sites of the body.5,6Several process may contribute to the subclinical inflammatory state of individuals with obesity. These include accumulation of reactive oxygen species, poor oxygen consumption, low oxygen tension, and induction of endoplasmic reticulum stress.7,8These preexisting states can make obese people more vulnerable to some viruses particularly those who OT-R antagonist 1 utilize these mechanisms to promote viral pathogenesis.9,10 With the ongoing COVID19 pandemic, several studies demonstrated obesity as a risk issue to develop severe COVID19 symptoms and complications (e.g., hospitalization, rigorous care unit admission, requirement of mechanical ventilation, and death).11,12,13,14Interestingly, this occurs independently OT-R antagonist 1 of other factors that are usually tightly related to obesity (e.g., diabetes mellitus and cardiovascular disorders). It is not entirely obvious how increased BMI may promote adverse COVID19 outcomes. However, impaired production of proinflammatory cytokines, infiltration of innate immune cells, and suppression of T and B lymphocyte functions may contribute to viralinduced immunopathology, uncontrolled pulmonary inflammation, and respiratory tissue damage.15,16,17,18Hyperglycemia and hyperinsulinemia in obese people were found to OT-R antagonist 1 reduce the inflammatory potential and promote the immunosenescence of the CD4 and CD8 compartments which may render these individuals more vulnerable to the infection.15,16,17,18Hyperinsulinemia can also promote the viral uptake in adipocytes by upregulating the expression of GRP78 which serves as a binding cofactor of the viral spike (S) and the cellular receptor ACE2.15,16,17,18Thereby, several reports recommended prioritization of obese people to obtain COVID19 vaccination.11,19,20 However, because of the adverse effects of obesity and its tightly related condition diabetes mellitus on host immunity, there is a concern about the effectiveness of COVID19 vaccines among obese people.13,14,20,21In fact, this issue is not unique to COVID19 vaccinations, as previous reports demonstrated obesityassociated reduction of vaccine effectiveness to other viral infections (e.g., influenza and hepatitis B viruses).22,23To our best of knowledge, there is currently a lack of focused reports about this issue in COVID19 vaccination settings. Some previous studies had obese individuals among their study population, but these studies did not intensively investigate whether obesity affects COVID19 vaccine effectiveness.24,25,26,27,28Moreover, immunoassays that only determine the presence of antiSARSCoV2 antibodies, but do not assess their neutralizing activity, were utilized in most of these studies. Hence, we aimed to investigate the effectiveness of numerous Sbased COVID19 vaccines in inducing antiS IgG antibodies among individuals with numerous classes of obesity (class I, II, III, and super obesity). The neutralizing activity of these antibodies was determined by serumneturalization test (SNT) utilizing a local SARSCoV2 isolate. Antinucleocapsid (NP) was also assessed, in addition to obtaining participants’ history of past COVID19 molecular diagnosis, to differentiate between acquired immunity via vaccination only or though vaccination and recovery from past contamination. == 2. MATERIALS AND METHODS == == 2.1. Clinical samples == This study aimed to investigate the effectiveness of COVID19 vaccines among individuals older than 18 with obesity (BMI 30 kg/m2) who received two doses of COVID19 vaccine. To provide a sidebyside comparison, those with normal BMI were also invited to participate in the study. Voluntary participants were asked to sign an informed consent, fill in a questionnaire, and provide a serum sample. The questionnaire included questions about participant demographics such as age, gender, height,.

Our study is also limited by the relatively small number of samples considering the large heterogenicity of the study subject