BNT162b2 induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 diminish with age

Each novel SARS-CoV-2 variant renews concerns about decreased vaccine efficacy caused by evasion of vaccine induced neutralizing antibodies. However, accumulating epidemiological data show that while vaccine prevention of infection varies, protection from severe disease and death remains high. Thus, immune responses beyond neutralization could contribute to vaccine efficacy. Polyclonal antibodies function through their Fab domains that neutralize virus directly, and Fc domains that induce non-neutralizing host responses via engagement of Fc receptors on immune cells. To understand how vaccine induced neutralizing and non-neutralizing activities synergize to promote protection, we leverage sera from 51 SARS-CoV-2 uninfected health-care workers after two doses of the BNT162b2 mRNA vaccine. We show that BNT162b2 elicits antibodies that neutralize clinical isolates of wildtype and five variants of SARS-CoV-2, including Omicron BA.2, and, critically, induce Fc effector functions. Fc{gamma}RIIIa/CD16 activity is linked to neutralizing activity and associated with post-translational afucosylation and sialylation of vaccine specific antibodies. Further, neutralizing and non-neutralizing functions diminish with age, with limited polyfunctional breadth, magnitude and coordination observed in those [≥]65 years old compared to <65. Thus, studying Fc functions in addition to Fab mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations such as the elderly against SARS-CoV-2 and novel variants.

Cellular and humoral Immune response to mRNA COVID-19 vaccination in subjects with chronic lymphocytic leukemia

Chronic Lymphocytic Leukemia (CLL) is predominantly a B-lymphocyte leukemia associated with immune defects that are often exacerbated by CLL directed therapies. SARS-CoV-2 infection poses a significant risk of illness or mortality to CLL patients, and while SARS-CoV-2 vaccines are highly effective in immunocompetent individuals, efficacy varies substantially in immunocompromised patients, including those with CLL. To date, studies of COVID-19 vaccine immune responses in immunocompromised hosts have largely relied on semi-quantitative antibody titers that only partially characterize vaccine-elicited immune responses and do not measure B or T-cell specific responses that may also play a protective role in vaccinees. Here, we report RBD-specific antibody as well as B-cell and T-cell responses in an observational cohort of sixteen CLL subjects who received mRNA vaccination against SARS-CoV-2, finding a strong association between CLL treatment and vaccine immunogenicity, with important implications for vaccination timing in the context of CLL treatment or recovery from prior treatment.

Previously infected vaccinees broadly neutralize SARS-CoV-2 variants

We compared the serum neutralizing antibody titers before and after two doses of the BNT162b2 COVID-19 vaccine in ten individuals who recovered from SARS-CoV-2 infection prior to vaccination to 20 individuals with no history of infection, against clinical isolates of B.1.1.7, B.1.351, P.1, and the original SARS-CoV-2 virus. Vaccination boosted pre-existing levels of anti-SARS-CoV-2 spike antibodies 10-fold in previously infected individuals, but not to levels significantly higher than those of uninfected vaccinees. However, neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees against every variant tested: 5.2-fold against B.1.1.7, 6.5-fold against B.1.351, 4.3-fold against P.1, and 3.4-fold against original SARS-CoV-2. Our study indicates that a first-generation COVID-19 vaccine provides broad protection from SARS-CoV-2variants in individuals with previous infection.

Neutralization of SARS-CoV-2 variants by convalescent and vaccinated serum

We tested human sera from large, demographically balanced cohorts of BNT162b2 vaccine recipients (n=51) and COVID-19 patients (n=44) for neutralizing antibodies against SARS-CoV-2 variants B.1.1.7 and B.1.351. Although the effect is more pronounced in the vaccine cohort, both B.1.1.7 and B.1.351 show significantly reduced levels of neutralization by vaccinated and convalescent sera. Age is negatively correlated with neutralization in vaccinee, and levels of variant-specific RBD antibodies are proportional to neutralizing activities.

Hepatitis C virus infection among people who inject drugs in Bangkok, Thailand, 2005–2010

Background Approximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). Newdirect-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patientsand are becoming available in countries around the world. To prepare for new HCV treatment optionsin Thailand, this study characterized HCV infections among people who inject drugs (PWID) inBangkok.Methods The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted amongPWID, 2005–2013. Blood specimens were randomly selected from PWID screened for the BTS, to testfor anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction,using multiplex primer sets with unique identifier sequences; amplification products were pooled in setsof 25; and consensus sequencing was performed to characterize individual HCV genotypes.Results The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016(82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjustedodds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4–4.3), those aged 40 years or older (aOR 2.7,95% CI 2.1–3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4–2.1),and those who tested HIV positive (aOR 5.2, 95% CI 3.7–7.4). HCV RNA was detected in 644(81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalenceof 36.0% (95% CI 33.8–38.2). Among a random sample of 249 of the 644 specimens, 218 could becharacterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b(6.9%) and 6n (8.7%).Conclusion The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third(36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As thegovernment of Thailand considers introduction of direct-acting antiviral medications for people withhepatitis C, it will be important to ensure that the medications target these subtypes.