Developing the concept of beneficial non-specific effect of live vaccines with epidemiological studies

Abstract

Background and objectives Epidemiological and immunological studies are increasingly reporting non-specific effects (NSEs) of vaccines; i.e. vaccines may affect the risk and severity of non-targeted infections. We reviewed how epidemiological studies developed the concept of beneficial NSEs of live vaccines. Sources This is a personal narrative of how we came to pursue the concept of NSEs in studies of measles vaccine (MV) from the late 1970s. We also searched Pubmed for epidemiological studies of non-specific/nonspecific effects (NSEs) of the most common human vaccines. Content When smallpox vaccine was introduced around 1800, BCG against tuberculosis in the 1920s and oral polio vaccine (OPV) in the 1960s, there were suggestions that these live attenuated vaccines reduced mortality more than expected. However, scientific follow-up was limited and the concept of beneficial NSEs did not become mainstream. We observed beneficial NSEs after MV was introduced in low-income countries in the 1970s. Subsequent observational studies and randomised trials confirmed beneficial NSEs of smallpox vaccine, BCG and OPV. Recently, beneficial NSEs have been claimed for the non-live diphtheria-tetanus-pertussis and rabies vaccines. However, no non-live vaccine has yet been documented to produce beneficial NSEs. Implications Observational and experimental research has shown beneficial NSEs of four live attenuated vaccines, smallpox vaccine, BCG, OPV and MV. With immunological evidence now supporting the epidemiological observations, it is urgent to take both the specific and NSEs into account in the planning of vaccination programs.

Does BCG protect against SARS-CoV-2 infection ?: elements of proof

“…However, numerous immunological studies have concluded that a vaccine can have a non specific protective effect. 1 At the beginning of the 20 th century, Calmette already noted that children vaccinated with BCG had a lower mortality rate 1 . Since then may have been born the principle of non specific effects of BCG vaccine.…”

“…This means that it may have effects on infections not targeted by the vaccine. 1 Observationl studies found that Bacillus Calmette Guerin (BCG) vaccination is associated with reduced non specific mortality and better survival 1 . Other immunological studies demonstrated that BCG can induce trained innate immuniy.…”

Heterologous effects of vaccination and trained immunity

“…In this issue of CMI, five narrative reviews offer recent insights on innate and adaptive immune memory, shedding light on specific and nonspecific effects of vaccines against a variety of pathogens. Benn and Aaby [9] describe in an historical review how epidemiologic studies in many industrialized and low-income countries led to the concept of beneficial nonspecific effects of BCG and other live human vaccines. Koeken et al [10] discuss the epidemiologic evidence and biologic concepts of early clearance of M. tuberculosis by BCG vaccination.…”

Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses

“…This feature in the SARS-CoV-2 protein sequence may be a pointer to support the idea of using the MMR vaccine in COVID-19 as floated by Fidel and Noverr [15] and the use of recombinant ACE2 by Kruse [16] as a preventive measure to reduce the inflammation in COVID-19 patients. The use of drugs/vaccines for existing viruses in managing untreatable viral diseases has been suggested by others also [17,18] including for COVID-19 [19].…”