Dual pattern recognition receptor ligands CL401, CL413, and CL429 as adjuvants for inactivated chikungunya virus.

Chikungunya virus (CHIKV) is responsible for incapacitating joint pains and is a significant health hazard in many countries. Though a definite need for a CHIKV vaccine is felt, long disappearance of CHIKV from circulation in humans has been a concern for vaccine development. Use of two separate pattern recognition receptor ligands has been shown to enhance immune response to the administered antigen. In addition, intradermal delivery of vaccine tends to mimic the natural mode of CHIKV infection. Therefore, in this study, we explored whether intradermal and intramuscular immunization with inactivated CHIKV (I-CHIKV) supplemented with dual pattern-recognition receptor ligands, CL401, CL413, and CL429, is an effective approach to enhancing antibody response to CHIKV. Our in vivo data show that I-CHIKV supplemented with these chimeric PRR ligands induces enhanced neutralizing antibody response after intradermal delivery, but is less efficient after intramuscular immunization. These results suggest that intradermal delivery of I-CHIKV with chimeric adjuvants is a possible way to elicited a better antibody response.

Immunogenicity of two COVID-19 vaccines used in India: An observational cohort study in health care workers from a tertiary care hospital.

COVID-19 pandemic witnessed rapid development and use of several vaccines. In India, a country-wide immunization was initiated in January 2021. COVISHIELD, the chimpanzee adenoviral-vectored vaccine with full-length SARS-COV-2 spike insert and COVAXIN, the whole virus-inactivated vaccines were used. To assess and compare immune response of health-care-workers to COVISHIELD (n=187) and COVAXIN (n=21), blood samples were collected pre-vaccination, 1month post-1/post-2 doses and 6months post-dose-2 and tested for IgG-anti-SARS-CoV-2 (ELISA) and neutralizing (Nab,PRNT50) antibodies. Spike-protein-specific T cells were quantitated by IFN-γ-ELISPOT. In pre-vaccination-antibody-negative COVISHIELD recipients (pre-negatives, n=120), %Nab seroconversion (median, IQR Nab titers) increased from 55.1% (16, 2.5-36.3) post-dose-1 to 95.6% (64.5, 4.5-154.2, p<0.001) post-dose-2 that were independent of age/gender/BMI. Nab response was higher among pre-positives with hybrid immunity at all-time points (p<0.01-0.0001) and independent of age/gender/BMI/Comorbidities. Post-dose-2-seroconversion (50%, p<0.001) and Nab titers (6.75, 2.5-24.8, p<0.001) in COVAXIN-recipients were lower than COVISHIELD. COVAXIN elicited a superior IFN-γ-T cell response as measured by ELISPOT (100%; 1226, 811-1532 spot forming units, SFU/million PBMCs v/s 57.8%; 21.7,1.6-169.2; p<0.001). At 6months, 28.3% (15/53) COVISHIELD and 3/3COVAXIN recipients were Nab-negative. T cell response remained unchanged. During immunization, COVID-19 cases were detected among COVISHIELD (n=4) and COVAXIN (n=2) recipients. At 6months, 9cases were recorded in COVISHIELD-recipients. This first-time, systematic, real-world assessment and long-term follow up revealed generation of higher neutralizing antibody titers by COVISHIELD and stronger T-cell response by COVAXIN. Diminished Nab titers at 6months emphasize early booster. Immunogenicity/efficacy of vaccines will change with the progression of the pandemic needing careful evaluations in the field-settings.

Disease-duration based comparison of subsets of immune cells in SARS CoV-2 infected patients presenting with mild or severe symptoms identifies prognostic markers for severity.

INTRODUCTION: Infection with SARS-CoV-2 leads to a spectrum of symptoms. Understanding the basis for severity remains crucial for better management and therapy development. So far, older age, associated-comorbidities, and IL-6 have been associated with severity/mortality. MATERIALS AND METHODOLOGY: As a primary step, we analyzed the frequency and functional profile of innate immune cells (NK cells/dendritic cells/monocytes) and adaptive immunity-driving lymphocytes (B cells/T cells/follicular T helper cells) by flow cytometry. Sixty cases of SARS CoV-2 infection (25 severe, 35 mild) and ten healthy subjects without SARS CoV-2 IgG were included. Disease-duration based analysis of immune profile was explored for early events differentiating the two disease forms. Neutralizing antibody titers were determined by PRNT. RESULTS AND CONCLUSION: Disease severity was found to be associated with impaired maturation of mDCs and hyperactivation of NK, follicular T helper cells, and CD8 T cells. Lower IL-21 receptor expression on memory B cells indicated an imbalance in IL-21/IL-21 R ratio. Lower BCMA positive plasmablast cells in severe cases did suggest a probable absence of long-term humoral immunity. Multivariate analysis revealed a progressive association of PD-1+CD4 T cells with PRNT50 titers. Thus, in addition to identifying probable prognostic markers for severity, our study emphasizes the definite need for in-depth viral antigen-specific functional analyses in a larger patient cohort and with multiple sampling.

Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age.

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.