BCG strain modulates the ontogeny of mycobacterial-specific and heterologous T cell immunity to vaccination in infants
DOI members who co-authored the paper were Anna-Ursula Happel, Trishana Nundalall, Jerome Wendoh, Nobomi Dontsa, Olatogni Berenice Alinde, Heather B. Jaspan and Clive Gray.
Various Bacille Calmette-Guerin (BCG) vaccine strains are used worldwide and differences in their immunogenicity and efficacy have been reported. BCG may also provide protection against off-target antigens, so Dr Kiravu and the team of researchers utilised two African birth cohorts to identify the impact of different BCG strains on the ontogeny of vaccine-specific and heterologous vaccine immunogenicity in the first 9 months of life.
“A total of 270 infants were studied: 84 from Jos, Nigeria (vaccinated with BCG-Bulgaria) and 187 from Cape Town, South Africa (154 vaccinated with BCG-Denmark and 33 with BCG-Russia). Infant whole blood was taken at birth, 7, 15, and 36 weeks and short-term stimulated (12 h) in vitro with BCG, Tetanus and Pertussis antigens. Using multiparameter flow cytometry, CD4+ T cell memory subset polyfunctionality was measured by analysing permutations of TNF-α, IL-2, and IFN-γ expression at each time point. Data was analysed using FlowJo, SPICE, R, and COMPASS”.
The researchers compared BCG-Bulgaria, BCG-Russia and BCG-Denmark. They found that babies vaccinated with BCG-Denmark had higher frequencies of BCG-stimulated CD4+ T cell responses peaking at week 7 after immunization and had durable polyfunctional CD4+ T cells that were in an earlier differentiated memory stage compared to BCG-Bulgaria and BCG-Russia. The latter responses had lower polyfunctional scores and tended to accumulate in CD4+ T cells naïve-like state (CD45RA+CD27+). BCG-Denmark vaccination also resulted in higher amounts of polyfunctional cytokine responses to heterologous vaccine antigens (Tetanus and Pertussis).
Agano Kiravu and the team’s data showed that the “BCG strain was the strongest determinant of both BCG-stimulated and heterologous vaccine stimulated T cell magnitude and polyfunctionality”. Their findings may influence vaccine policy, manufacture and immunization programs. They suggest that BCG-Denmark (the first vaccine many African infants receive) has both specific and off-target effects in the early months of an infant’s life which could assist in priming to other EPI vaccines.
Read the paper - BCG Vaccine Strain Modulates the Ontogeny of Both Mycobacterial-Specific and Heterologous T Cell Immunity to Vaccination in Infants
Article by Bonamy Holtak