Background: We earlier showed that 4-phenylbutyrate (PB) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D₃ in a lung epithelial cell line. We aimed to evaluate a therapeutic dose of PB alone or in combination with vitamin D₃ for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (MDM). Methods: Healthy volunteers were enrolled in an 8-days open trial with three doses of PB [250 mg (Group-I), 500 mg (Group-II) or 1000 mg (Group-III)] twice daily (b.d.) together with vitamin D₃ {5000 IU once daily (o.d.)}, PB (500 mg b.d.) (Group-IV) or vitamin D₃ (5000 IU o.d.) (Group-V), given orally for 4 days. Blood was collected on day-0, day-4 and day-8; plasma was separated, peripheral blood mononuclear cells (PBMC), non-adherent lymphocytes (NAL) and MDM were cultured. LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA, respectively. In plasma, 25-hydorxyvitamin D₃ levels were determined by ELISA. MDM-mediated killing of Mycobacterium tuberculosis (Mtb) (H37Rv) was performed by conventional culture method. Results: MDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4, while Group-I showed increased transcript at day-4 and day-8 compared to day-0 (p < 0.05). Both Group-I and -II exhibited higher levels of transcript on day-4 compared to Group-III and Group-V (p < 0.035). Increased induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV (p < 0.05), while Group-IV showed increased levels on day-8 compared to Group-I and Group-III (p < 0.04). Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I, -II and -V (p < 0.05). Conclusion: The results demonstrate that 500 mg b.d. PB with 5000 IU o.d. vitamin D₃ is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages. Hence, this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB (NCT01580007).

Background: The adaptive immune response is a crucial component of the protective immunity against SARS-CoV-2, generated after infection or vaccination. Methods: We studied antibody titers, neutralizing antibodies and cellular immune responses to four different COVID-19 vaccines, namely Pfizer-BioNTech, Moderna Spikevax, AstraZeneca and Sinopharm vaccines in the Bangladeshi population (n = 1780). Results: mRNA vaccines Moderna (14,655 ± 11.3) and Pfizer (13,772 ± 11.5) elicited significantly higher anti-Spike (S) antibody titers compared to the Adenovector vaccine AstraZeneca (2443 ± 12.8) and inactivated vaccine Sinopharm (1150 ± 11.2). SARS-CoV-2-specific neutralizing antibodies as well as IFN-γ-secreting lymphocytes were more abundant in Pfizer and Moderna vaccine recipients compared to AstraZeneca and Sinopharm vaccine recipients. Participants previously infected with SARS-CoV-2 exhibited higher post-vaccine immune responses (S-specific and neutralizing antibodies, IFN-γ-secreting cells) compared to uninfected participants. Memory B (B_MEM), total CD8⁺T, CD4⁺ central memory (CD4⁺_CM) and T-regulatory (T_REG) cells were more numerous in AstraZeneca vaccine recipients compared to other vaccine recipients. Plasmablasts, B-regulatory (B_REG) and CD4⁺ effector (CD4⁺_EFF) cells were more numerous in mRNA vaccine recipients. Conclusions: mRNA vaccines generated a higher antibody response, while a differential cellular response was observed for different vaccine types, suggesting that both cellular and humoral responses are important in immune monitoring of different types of vaccines.

We demonstrated in a randomized placebo-controlled trial that WRSS1, a live oral Shigella sonnei vaccine candidate, is safe in Bangladeshi adults and children, and elicits antigen-specific antibodies. Here, we describe functional antibody and innate immune responses to WRSS1. Adults (18–39 years) and children (5–9 years) received 3 doses of 3 × 10⁵ or 3 × 10⁶ colony forming units (CFU) of WRSS1 or placebo, 4 weeks apart; children additionally received 3 × 10⁴ CFU. Blood and stool were collected at baseline and 7 days after each dose. Functional antibodies were measured using serum bactericidal antibody (SBA) assay. Cytokine/chemokine concentrations were measured in lymphocyte cultures. Host defense peptides LL-37, HBD-1, and HD-5 were analyzed in plasma and stool. Children showed increased SBA titers over baseline after the third dose of 3 × 10⁶ CFU (P = .048). Significant increases of Th-17 and proinflammatory cytokines (TNF-α, G-CSF, MIP-1β), and reduction of anti-inflammatory and Th2 cytokines (IL-10, IL-13, GM-CSF) were observed in children. Plasma HBD-1 and LL-37 decreased in children after vaccination but were increased/unchanged in adults. Functional antibodies and Th1/Th17 cytokine responses in children may serve as important indicators of immunogenicity and protective potential of WRSS1. Clinical Trials Registration: NCT01813071.

COVID-19 vaccines have been effective in preventing severe illness, hospitalization and death, however, the effectiveness diminishes with time. Here, we evaluated the longevity of antibodies generated by COIVD-19 vaccines and the risk of (re)infection in Bangladeshi population. Adults receiving two doses of AstraZeneca, Pfizer, Moderna or Sinopharm vaccines were enrolled at 2–4 weeks after second dosing and followed-up at 4-monthly interval for 1 year. Data on COVID-like symptoms, confirmed COVID-19 infection, co-morbidities, and receipt of booster dose were collected; blood was collected for measuring spike (S)- and nucleocapsid (N)-specific antibodies. S-specific antibody titers reduced by ~ 50% at 1st follow-up visit and continued to decline unless re-stimulated by booster vaccine dose or (re)infection. Individuals infected between follow-up visits showed significantly lower S-antibody titers at preceding visits compared to the uninfected individuals. Pre-enrolment infection between primary vaccination dosing exhibited 60% and 50% protection against reinfection at 5 and 9 months, respectively. mRNA vaccines provided highest odds of protection from (re)infection up to 5 months (Odds Ratio (OR) = 0.08), however, protection persisted for 9 months in AstraZeneca vaccine recipients (OR = 0.06). In conclusion, vaccine-mediated protection from (re)infection is partially linked to elevated levels of S-specific antibodies. AstraZeneca vaccine provided the longest protection.

Chromobacterium violaceum is a Gram-negative bacterium, found in tropical and subtropical regions. C. violaceum infection rarely occurs, but once occurs, it is associated with significant mortality due to severe systemic infection. Since the first human case from Malaysia in 1927, >150 cases of C. violaceum infection have been reported worldwide. We have described here a fatal case of C. violaceum infection in a tertiary care hospital in Dhaka, Bangladesh. To the best of our knowledge, this is the first case of C. violaceum infection in Bangladesh.