Heterologous vaccine interventions: boosting immunity against future pandemics

While vaccines traditionally have been designed and used for protection against infection or disease caused by one specific pathogen, there are known off-target effects from vaccines that can impact infection from unrelated pathogens. The best-known non-specific effects from an unrelated or heterologous vaccine are from the use of the Bacillus Calmette-Guérin (BCG) vaccine, mediated partly through trained immunity. Other vaccines have similar heterologous effects. This review covers molecular mechanisms behind the heterologous effects, and the potential use of heterologous vaccination in the current COVID-19 pandemic. We then discuss novel pandemic response strategies based on rapidly deployed, widespread heterologous vaccination to boost population-level immunity for initial, partial protection against infection and/or clinical disease, while specific vaccines are developed.

Cross-Reactive Effects of Vaccines: Heterologous Immunity between Tetanus and Chlamydia

Vaccines can have heterologous effects on the immune system, i.e., effects other than triggering an immune response against the disease targeted by the vaccine. We investigated whether monoclonal antibodies (mAbs) specific for tetanus could cross-react with Chlamydia and confer heterologous protection against chlamydial infection. The capability of two tetanus-specific mAbs, namely mAb26 and mAb51, to prevent chlamydial infection has been assessed: (i) in vitro, by performing a neutralization assay using human conjunctival epithelial (HCjE) cells infected with Chlamydia trachomatis serovar B, and (ii) in vivo, by using a guinea pig model of Chlamydiacaviae-induced inclusion conjunctivitis. The mAb26 has been superior in comparison with mAb51 in the prevention of chlamydial infection in HCjE cells. The mAb26 has conferred ≈40% inhibition of the infection, compared to less than 5% inhibition in the presence of the mAb51. In vivo, mAb26 significantly diminished ocular pathology intensity in guinea pigs infected with C. caviae compared to either the mAb51-treated or sham-treated guinea pigs. Our data provide insights that tetanus immunization generates antibodies which induce heterologous chlamydial immunity and promote protection beyond the intended target pathogen.