We could soon have one vaccine for Covid and monkeypox

On July 23, WHO declared monkeypox a Public Health Emergency of International Concern (PHEIC), its highest level of alert. Since Covid in February 2020, this is the second such alert in two years. This international monkeypox outbreak is largely restricted to those below 40 years of age, born after smallpox vaccination ended in 1980.The history of vaccination is linked to that of smallpox. In common folklore, modern vaccination came into being on May 14, 1796 when Edward Jenner used pus from a cowpox pustule on the hand of milkmaid Sarah Nelmes to inoculate 8-year-old James Phipps and protect him from smallpox. Ancient variolation to now: However, an ancient method called ‘variolation’ was already being practised for centuries in India, China, and the Orient. This involved introducing a tiny amount of pus from the smallpox pustule into the recipient’s arm. If done well, it produced one pox at the site and protected from smallpox. If not done well, it caused widespread infection, painful disease and 2-3% mortality. Variolation was an art!Lady Mary Wortley Montagu was an English aristocrat, writer and poet, and also wife of the British ambassador to the Ottoman Empire in 1716. She wrote about her travels there in the Turkish Embassy Letters. She also learned the art of variolation and introduced it to 18th century Britain. Though Jenner’s is “a compelling story of beautiful milkmaids, eureka moments and ethically questionable experiments”, it was a local surgeon in Gloucestershire, John Fewster, who serendipitously discovered cross-protection between cowpox and smallpox in 1763. However, it was Jenner who understood the implications of this revolutionary medical advance and predicted in 1801 that vaccination would rid the world of smallpox. It took another 180 years for his prophecy to be realised. medium93377373For over a 100 years since Jenner, smallpox vaccination went from ‘arm to arm’ in humans. In 1860 scientists in France and Italy started using animals – initially cows but later sheep, horses, and donkeys – to amplify the smallpox vaccine. We now know that maintaining viruses in non-natural hosts over multiple generations changes them in unpredictable ways. By the 1930s, the smallpox vaccine cocktail largely included a virus called ‘vaccinia’, whose origin and animal reservoir remain unknown to this day. Due to its cross-protective immunity, this live vaccinia virus was used to eradicate smallpox and it saved millions of lives.The first-generation smallpox vaccine was made by growing vaccinia virus in the skin of animals – mostly cows, but also sheep. The second-generation vaccine used live vaccinia virus grown in eggs or in cell culture, being introduced in the late 1950s and early 1970s, respectively. A freeze-drying method developed in the early 1950s allowed the vaccine to be stored and transported at room temperature. Between 1958 and 1977 it was mainly the second-generation vaccine that was used in smallpox eradication programmes. Third-generation vaccines introduced in the late 1970s are based on a Turkish strain – Modified Vaccinia Ankara (MVA) – which had lost the ability to multiply in humans; it could still be grown well in chicken embryos. The smallpox-monkeypox vector: Two smallpox vaccines are approved for use against monkeypox. * ACAM2000 is a second-generation vaccine that includes live vaccinia virus, which replicates in the recipient and has unpleasant side effects. * MVA-BN is a third-generation vaccine, which uses MVA and has a better safety profile. It is licensed under three brand names – Jynneos (US), Imvanex (EU) and Imvamune (Canada).Bernard Moss, a Senior Investigator at the National Institutes of Health, US, developed MVA technology in the 1990s as a vehicle for engineering other novel vaccines. A vaccine for rabies in current clinical use was developed using this technology. Moss and others have also exploited MVA to develop vaccine candidates against HIV/AIDS. Rama Rao Amara, a Professor at the Emory Vaccine Centre in Atlanta, US has spent over two decades working with MVA to make an AIDS vaccine. In 2007, he and Moss showed durable protection in monkeys against SIV – a simian cousin of the human immunodeficiency virus (HIV). They also demonstrated protection against monkeypox in animals vaccinated with their MVA-HIV candidates. The monkeypox-Covid vector: In a 2008 study, Moss showed that monkeys could be protected from monkeypox with just one dose of either MVA or the ACAM2000 vaccine. In 2019 a clinical study showed equivalence between the MVA and ACAM2000 vaccines, with the former showing better post-vaccination safety. Thus, several studies have established MVA-based candidates to have good efficacy against monkeypox. This brings us to MVA/S: MVA-based Covid vaccines that express the viral Spike protein. In a study published in March 2021, Amara showed that MVA/S vaccination produced strong neutralising antibodies and cellular immunity against the Covid virus. The vaccine also protected monkeys from infection and lung pathology, including inflammation, which is the main cause of Covid-related mortality. Would MVA/S protect against both Covid and monkeypox? Those experiments haven’t been done yet. But considering Amara’s results and the established efficacy of MVA against monkeypox, that is likely to be the case. MVA/S would be a very attractive candidate for clinical testing. A single vaccine that can protect against two diseases – both circulating now – both with a PHEIC rating – would be historic and innovative.The writer is a virologist and Fellow at OCIS and Green Templeton College, University of Oxford