Augmenting Vaccine Efficacy against Delta Variant with ‘Mycobacterium-<i>w</i>’-Mediated Modulation of NK-ADCC and TLR-MYD88 Pathways
Sarita Rani Jaiswal,
Ashraf Saifullah,
Jaganath Arunachalam,
Rohit Lakhchaura,
Dhanir Tailor,
Anupama Mehta,
Gitali Bhagawati,
Hemamalini Aiyer,
Subhrajit Biswas,
Bakulesh Khamar,
Sanjay V. Malhotra,
Suparno Chakrabarti
Affiliations
Sarita Rani Jaiswal
Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, New Delhi 110096, India
Ashraf Saifullah
Department of Blood and Marrow Transplantation, Dharamshila Narayana Super-Speciality Hospital, New Delhi 110096, India
Jaganath Arunachalam
Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, New Delhi 110096, India
Rohit Lakhchaura
Department of Blood and Marrow Transplantation, Dharamshila Narayana Super-Speciality Hospital, New Delhi 110096, India
Dhanir Tailor
Department of Cell, Development & Cancer Biology and Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA
Anupama Mehta
Department of Blood and Marrow Transplantation, Dharamshila Narayana Super-Speciality Hospital, New Delhi 110096, India
Gitali Bhagawati
Department of Pathology and Microbiology, Dharamshila Narayana Super-Speciality Hospital, New Delhi 110096, India
Hemamalini Aiyer
Department of Pathology and Microbiology, Dharamshila Narayana Super-Speciality Hospital, New Delhi 110096, India
Subhrajit Biswas
Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida 201313, India
Bakulesh Khamar
Research & Development, Cadila Pharmaceuticals Ltd., Ahmedabad 382225, India
Sanjay V. Malhotra
Department of Cell, Development & Cancer Biology and Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA
Suparno Chakrabarti
Cellular Therapy and Immunology, Manashi Chakrabarti Foundation, New Delhi 110096, India
Mycobacterium-w (Mw) was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw + ChAdOx1 group) were monitored for symptomatic COVID-19 during a major outbreak with the delta variant of SARS-CoV-2 (April–June 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in the Mw + ChAdOx1 group, only two had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p = 0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw + ChAdOx1 group, along with downregulation of the TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
