Benzinga | Dec 4, 2020 08:03AM EST

Tonix Pharma Highlights Independent Researchers Reported 99.7% Colinear Identity Between A Circa 1860 US Smallpox Vaccine And Horsepox Virus

Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, announced today that independent researchers reported 99.7% colinear identity between a circa 1860 U.S. smallpox vaccine and horsepox virus. Tonix's TNX-801 is a horsepox-based live virus vaccine being developed as a potential vaccine to prevent smallpox and monkeypox. Tonix's TNX-801 is also the vector on which Tonix's COVID-19 experimental vaccine is based. Tonix was not involved in the research reported.

The publication in the Journal Genome Biology, entitled "Re-assembly of 19th-century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the United States"1 analyzed sequences of U.S. smallpox vaccines that had been published recently by a different group also in Genome Biology, entitled "The origins and genomic diversity of American Civil War Era smallpox vaccine strains"2. The first paper applied modern techniques of sequencing old DNA to smallpox vaccine specimens stored in the M?tter Museum in Philadelphia, and identified that vaccines with horsepox core viral sequences were used in the 1860's and referenced sequence information from several vaccines that the authors posted in GenBank, the National Institute of Health genetic sequence database. The new report re-assembled certain genomes from the GenBank sequences associated with the first paper and found a remarkable degree of identity with the circa 1860 U.S. smallpox vaccine VK05 and the 1976 Mongolian horspox isolate called MNR-76. Tonix's TNX-801 was synthesized3 based on the sequence of the Mongolian horsepox isolate MNR-764.

"The extent of colinear identity, approximately 99.7%, is remarkable between the circa 1860 U.S. smallpox vaccine VK05 and the 1976 Mongolian horsepox genome," said, Jos? Esparza, MD, PhD, Adjunct Professor at the Institute of Human Virology, School of Medicine of the University of Maryland, who was an author of the Genome Biology letter. "This finding indicates that a true horsepox virus was used as a smallpox vaccine in the U.S. in the 1860's. It is astonishing that there are so few differences between these viruses despite the separation of their isolation by over 100 years and from different continents."

"This recent discovery is another step in establishing that what is called 'horsepox' today was used to vaccinate against smallpox in the 19th century," said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. "Dr. Edward Jenner invented vaccination in 1798 and the procedure was called vaccination because the inoculum material was initially obtained from lesions on the udders of cows affected by a mild disease known as cowpox. 'Cow' is 'vacca' in Latin. However, Dr. Jenner suspected that cowpox originated from horsepox.5 Subsequently, Dr. Jenner and others immunized against smallpox using material directly obtained from horses. The use of vaccines from horses was sometimes called 'equination' from the Latin 'equus' which means 'horse'. Equination and vaccination were practiced side-by-side in Europe6. Several years ago, we recognized that the 2006 genome sequence of the 1976 Mongolian horsepox4 may be more like the vaccines that Jenner used than modern vaccinia vaccines, because the modern vaccinia vaccines appear to have undergone both divergent and convergent evolution since Jenner's time. To recreate a vaccine similar to Jenner's, together with scientists at the University of Alberta, Canada, we synthesized3 a live horsepox virus based on the 1976 Mongolian horsepox virus sequence and we are developing it as a potential vaccine for smallpox and monkeypox, called TNX-801. Horsepox is also the vector for our COVID-19 vaccine, TNX-1800, which has been modified to direct the expression of CoV-2 spike protein."

"The new findings are particularly significant, because they confirm that horsepox has been used as a safe and effective smallpox vaccine since at least 1860, and probably since Edward Jenner's time in 1798," continued Dr. Lederman. "The new report confirms that modern 'vaccinia'-based smallpox vaccines from around the world have lost, apparently convergently, two genomic segments in evolution: an 11 Kilobase (kB) segment on the left side and a 6 kB Segment on the right side relative to the progenitor horsepox-like vaccines. The presence of these genetic elements in horsepox may contribute to the decreased virulence of horsepox relative to vaccinia in mice and the smaller plaque size in tissue culture. Later, after approximately 1875, when vaccinia propagation was moved from 'arm to arm' to growth on cows in 'vaccine farms'8, the core viral sequences of modern vaccinia vaccines appear to have diverged away from the horsepox core viral sequences. A standard for modern vaccine development and manufacturing is to make a 'master virus bank' and tie vaccine production to the exact properties of the original master virus bank. Edward Jenner did not keep a master virus bank, because his work pre-dated understanding of viruses by more than 100 years. However, the recent work on sequencing and analyzing archaic smallpox vaccines gives us a clearer understanding of the structure and features of Jenner's vaccines. The more we learn, the more we are led to believe that Jenner's vaccinia was either horsepox or more like horsepox than modern vaccinia vaccines."

The recent report is the latest in a series from a team composed by Dr. Esparza, Clarissa R Damaso, PhD at the Carlos Chagas Filho Biophisics Institute of the Federal University of Rio de Janeiro, Brazil, and Andreas Nitsche, Ph.D. at the Robert Koch Institute in Berlin, Germany. They have previously reported7 that the core viral sequence of a 1902 U.S. smallpox vaccine manufactured by Mulford, a vaccine manufacturer subsequently acquired by Merck, was closely related to the Mongolian horsepox MNR-76 on which TNX-801 is based. The latest report shows that the circa 1860 VK05 vaccine also contains a high degree of colinear identity through the ends of the viruses, including regions where all previously characterized smallpox vaccines including Mulford 1902 contained deletions of approximately 11 kB on the left side and 6 kB on the right side.

Dr. Lederman continued, "Smallpox was eradicated using single-dose live replicating vaccines that induce durable T cell immunity, prevent serious illness after infection and block forward transmission. Our hope and our goal is to produce vaccines that will provide long term immunity with a single dose using a proven technology that can be readily scaled up for manufacturing and that does not require a costly and cumbersome cold chain for distribution and storage."