Skip to main content
Premium Trial:

Request an Annual Quote

Smallpox Vaccine Strains From US Civil War Era Identified Through Metagenomic Sequencing

NEW YORK – During the time of the US Civil War, vaccinia virus strains were being used to inoculate people against smallpox, a new metagenomic sequencing analysis has found.

Vaccination efforts eradicated smallpox, which is caused by the variola virus, about 40 years ago, but prior to that, smallpox used to kill about a third of those infected. Following Edward Jenner's realization that exposure to cowpox could confer protection against smallpox, various source materials — cowpox, horsepox, and others — were used in smallpox vaccination efforts. These milder pathogens were introduced by applying pus or scabs from infected people into scratches or cuts to generate immunity.

Researchers from McMaster University have now analyzed viral traces left behind in vaccination kits from the Civil War era to determine what viruses were used at the time. Vaccination, they noted, was required of both Northern and Southern soldiers back then. As they reported in Genome Biology on Sunday, the researchers found that vaccinia virus strains were being propagated in people to be used in smallpox vaccination.

"Understanding the history, the evolution, and the ways in which these viruses can function as vaccines is hugely important in contemporary times," senior author Hendrik Poinar, director of the McMaster Ancient DNA Centre, said in a statement. "This work points to the importance of looking at the diversity of these vaccine strains found out in the wild." 

He and his colleagues generated metagenomic profiles of samples collected from both organic and non-organic parts of five vaccination kits from the Mütter Museum of the College of Physicians of Philadelphia's collection. These kits typically included lancets, small glass plates to mix fluids from the blisters of infected people, and tin boxes in which to collect scabs. 

While most of the shotgun sequencing data they generated was human, the researchers also uncovered a portion of sequence reads that mapped to the vaccinia virus.

Based on the human reads, the researchers could piece together mitochondrial genomes for three individuals. Their mitochondrial haplogroups are most common in west Eurasian, indicating the vaccine donors were of European ancestry. This finding surprised the researchers as they noted that, at the time, African-American children were often used to propagate vaccines in the southern US. 

Based on the proportion of reads mapping to the X chromosome or Y chromosome, two of the samples were from women, and the third was likely also from a woman, but with low-level contamination from a man.

By enriching the samples for reads from the Orthopoxvirus genus, the researchers focused on the viral data. For one sample, they were able to assemble a virus genome 185 kb in length de novo. However, for the four other samples, they did not have adequate data for de novo assemblies and instead generated consensus sequences.

A phylogenetic analysis of the viral samples in relation to other pox-family viruses placed the vaccine kit samples within the vaccinia virus clade. Indeed, the researchers noted the kit viruses clustered tightly, suggesting limited diversity in the vaccination strains in use in Philadelphia at the time. This suggests the vaccinia virus was circulating before the 20th century, the researchers noted. 

Together, these findings indicated that vaccination was still a bespoke process at the time with materials being passed from donors to patients.

The researchers further noted that the kit-derived strains grouped closely with another strain from Philadelphia from 1902 that was used in commercially generated vaccines.