Impact Of an Immune Modulator Mycobacterium-w On Adaptive Natural Killer Cells and Protection Against COVID-19

The kinetics of NKG2C+ adaptive natural killer (ANK) cells and NKG2A+inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied in a cohort of health-care workers following administration of heat killed Mycobacterium w (Mw group) in comparison to a control group. COVID-19 infection correlated with a lower NKG2C+ANK cells at baseline. NKG2C+ANK cells at baseline did not differ, but there was a significant upregulation of NKG2C expression and cytokine release in the Mw group (p=0.0009), particularly in those with lower baseline NKG2C expression (<15%), along with marked downregulation of NKG2A+iNK cells (p<0.0001), and an increase in the NKG2C+ANK/NKG2A+iNK ratio. This translated to a significant reduction in COVID-19 and its severity in the Mw group. No impact was observed on T cell subsets. Mw was observed to have a salutary impact on the ANK cell profile which might have provided protection against COVID-19 over a prolonged period in a non-immune high-risk population.

A randomised trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-1)

PurposeWe investigate whether Mycobacterium w (Mw), an immunomodulator, would improve clinical outcomes in coronavirus infectious disease 19 (COVID-19).MethodsWe conducted an exploratory, randomised, double-blind, placebo-controlled trial of hospitalised subjects with severe COVID-19 (pulmonary infiltrates and oxygen saturation ≤94% on room air) conducted at four tertiary care centers in India. Patients were randomised 1:1 to receive either 0.3 mL·day−1 of Mw intradermally or a matching placebo for three consecutive days. The primary outcome of the study was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The co-primary outcome was a change in SOFA score on days 7 and 14 compared to the baseline. The secondary outcomes were 28-day mortality, time to clinical recovery, time to RT-PCR negativity, adverse events, and othersResultsWe included 42 subjects (22 Mw, 20 placebo). On days 14 (OR, 30.4; 95% CI, 3.3–276.4) and 21 (OR, 14.9; 95% CI, 1.8–128.4), subjects in the Mw arm had a better clinical status distribution than placebo. There was no difference in the SOFA score change on days 7 and 14 between the two groups. We did not find any difference in the mortality, or other secondary outcomes. We observed no adverse events related to the use of Mw.ConclusionsThe use of Mw results in better clinical status distribution on days 14 and 21 compared to placebo in critically ill patients with COVID-19.

Leprosy vaccines – A voyage unfinished

Leprosy, a chronic granulomatous disease caused by Mycobacterium leprae, is endemic in many regions of the world. With introduction of multidrug therapy in 1982, there has been a dramatic reduction in the prevalence of leprosy, but new cases continue to appear. There have been more than 200,000 new cases per year for the past 10 years. There is a renewed interest in leprosy vaccines with immunoprophylactic and immunotherapeutic roles. Due to the difficulty in cultivating M. leprae in artificial media, vaccine strategies have centered on the use of cross-sensitizing mycobacteria. Bacillus Calmette–Guerin (BCG) has been the most popular among these, but with a widely varying protective efficacy reported from different parts of the world. In three meta-analyses, BCG has shown strong evidence of efficacy against leprosy. Recently, India has focused interest on another vaccine, Mycobacterium indicus pranii vaccine earlier known as Mycobacterium w. To overcome the limitations of these whole cell vaccines, various recombinant BCGs and subunit vaccines have been developed and studied in experimental models. These often yield inconsistent results. However, a new subunit recombinant vaccine – LepVax holds promise and has completed Phase 1a clinical trials successfully.

Innate Immune Response Modulation and Resistance to SARS-CoV-2 infection: A Prospective Comparative Cohort Study in High Risk Healthcare Workers

To evaluate ability of modulated innate immune response to provide resistance to development of symptomatic RT-PCR confirmed COVID-19, 96 inpatient front line health care workers (HCW) were cohorted in 1:2 ratio to receive TLR2 agonist (heat killed Mycobacterium w, Mw; n=32) as innate immune response modulator or observation (n=64). All were followed up for 100 days. The incidence of COVID-19 was 31 (32.3%) for the entire cohort, with only one developing COVID-19 in Mw group (3.1% vs 46.8%. protective efficacy - 93.33%, p=0.0001; 95% CI 53.3-99.1). Self-limiting local injection site reaction was the only side effect and was seen in 14 HCW. Findings from the study suggest the potential for providing resistance against novel pathogen like SARS-CoV-2 by modulating innate immune response.