Humoral correlate of vaccine-mediated protection from tuberculosis identified in humans and non-human primates.

Development of an effective tuberculosis (TB) vaccine has been challenged by incomplete understanding of specific factors that provide protection against (Mtb) and the lack of a known correlate of protection (CoP). Using a combination of samples from a vaccine showing efficacy (DarDar [NCT00052195]) and Bacille Calmette-Guerin (BCG)-immunized humans and nonhuman primates (NHP), we identify a humoral CoP that translates across species and vaccine regimens. Antibodies specific to the DarDar vaccine strain () sonicate (MOS) correlate with protection from the efficacy endpoint of definite TB.

COVID-19 vaccine responses are influenced by distinct risk factors in naive and SARS-CoV-2 experienced hemodialysis recipients.

Background: Clinical risk factors of deficient immune responses to COVID-19 mRNA vaccination in SARS-CoV-2 naive hemodialysis recipients (HDR) have already been identified. Clinical factors influencing hybrid immunity induced by SARS-CoV-2 infection and vaccination in HDR have not been reported.

Methods: A comprehensive analysis of antibody (Ab) and T cell responses to two doses of BNT162b2 mRNA vaccination was performed in 103 HDR, including 75 SARS-CoV-2 naive and 28 experienced patients, and in 106 healthy controls (HC) not undergoing HD, including 40 SARS-CoV-2 naive and 66 experienced subjects.

Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI.

Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown.

Positive-unlabeled learning to infer protection status and identify correlates in vaccine efficacy field trials.

Correlates of protection (CoPs) are key guideposts that both support vaccine development and licensure as well as improve our understanding of the attributes of immune responses that may directly provide protection. Unfortunately, factors such as low rate of exposure and low efficacy can result in low power to discover correlates in field trials-making it difficult to identify these guideposts for the pathogens against which there is greatest need for further insights. To address this gap, we examine the ability of positive-unlabeled (PU) learning approaches to use immunogenicity data and infection status outcomes to accurately predict protection status.

Sex- and species-associated differences in complement-mediated immunity in humans and rhesus macaques.

The complement system can be viewed as a "moderator" of innate immunity, "instructor" of humoral immunity, and "regulator" of adaptive immunity. While sex is known to affect humoral and cellular immune systems, its impact on complement in humans and rhesus macaques, a commonly used non-human primate model system, has not been well studied. To address this knowledge gap, we analyzed serum samples from 90 humans and 72 rhesus macaques for the abundance and activity of the complement system components.

Effector functions are required for broad and potent protection of neonatal mice with antibodies targeting HSV glycoprotein D.

Multiple failed herpes simplex virus (HSV) vaccine candidates induce robust neutralizing antibody (Ab) responses in clinical trials, raising the hypothesis that Fc-domain-dependent effector functions may be critical for protection. While neonatal HSV (nHSV) infection results in mortality and lifelong neurological morbidity in humans, it is uncommon among neonates with a seropositive birthing parent, supporting the hypothesis that Ab-based therapeutics could protect neonates from HSV. We therefore investigated the mechanisms of monoclonal Ab (mAb)-mediated protection in a mouse model of nHSV infection.

Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques.

The complement system can be viewed as a 'moderator' of innate immunity, 'instructor' of humoral immunity, and 'regulator' of adaptive immunity. While sex and aging are known to affect humoral and cellular immune systems, their impact on the complement pathway in humans and rhesus macaques, a commonly used non-human primate model system, have not been well-studied. To address this knowledge gap, we analyzed serum samples from 90 humans and 75 rhesus macaques for the abundance and activity of the complement system components.

Antibody effector functions are required for broad and potent protection of neonates from herpes simplex virus infection.

The failure of multiple herpes simplex virus (HSV) vaccine candidates that induce neutralizing antibody responses raises the hypothesis that other activities, such as Fc domain-dependent effector functions, may be critical for protection. While neonatal HSV (nHSV) infection result in mortality and lifelong neurological morbidity in humans, it is uncommon among neonates with a seropositive birthing parent, suggesting the potential efficacy of antibody-based therapeutics to protect neonates. We therefore investigated the mechanisms of monoclonal antibody (mAb)-mediated protection in a mouse model of nHSV infection.

Foundations for improved vaccine correlate of risk analysis using positive-unlabeled learning.

Insights into mechanisms of protection afforded by vaccine efficacy field trials can be complicated by both low rates of exposure and protection. However, these barriers do not preclude the discovery of correlates of reduced risk (CoR) of infection, which are a critical first step in defining correlates of protection (CoP). Given the significant investment in large-scale human vaccine efficacy trials and immunogenicity data collected to support CoR discovery, novel approaches for analyzing efficacy trials to optimally support discovery of CoP are critically needed.

Alteration of Tear Cytokine Expressions in Primary Acquired Nasolacrimal Duct Obstruction - Potential Insights into the Etiopathogenesis.

: To investigate the presence and level of 35 distinct cytokines in the tear fluid obtained from patients with primary acquired nasolacrimal duct obstruction (PANDO) and compare it with controls in an effort to understand the disease etiopathogenesis.: Standard protocols were used for collecting tears from 60 eyes (20 diseased eyes and 20 healthy fellow eyes of unilateral PANDO, 20 control eyes of healthy subjects). A total of 35 analytes involved in inflammation, angiogenesis and wound healing were assessed by multiplex ELISA.

De novo root transcriptome of a medicinally important rare tree Oroxylum indicum for characterization of the flavonoid biosynthesis pathway.

Oroxylum indicum (L.) Kurz is a medicinally important and rare tree species of the family Bignoniaceae. It is rich in flavonoid content and its mature roots are extensively used in Ayurvedic formulations.