Alumni Profile: Cal MacLennan

Green Templeton spoke to Professor Cal MacLennan (Clinical Medicine, 1989 and DPhil Neuroscience/Medicine, 1992) about his current work, wide-ranging career and time at then-Green College.

Cal works in the Global Health division of the Bill & Melinda Gates Foundation, where he leads the bacterial vaccine portfolios in Enteric and Diarrheal Diseases. His role focuses on vaccine product development for Shigella, which is responsible for dysentery and diarrhoeal disease, and for typhoid and other forms of Salmonella.

Shigella is the commonest cause of diarrhoeal death globally that lacks a vaccine. Although vaccine development has been underway for a 100 years, none has been licensed. Several promising candidate vaccines are currently in clinical trials. The most advanced are being trialled in Kenyan infants, with the intent that one or more will progress to a Phase 3 trial, the last trial before licensure and WHO prequalification. Cal said, ‘it will be exciting for me to see a first licenced Shigella vaccine, which we hope to have towards the end of this decade.

‘What is critical to understand is whether efficacy in European and North American adults can be replicated in children in low- and middle-income countries. We are now beyond just safety and immune responses to these vaccines – next are Phase 3 trials which will involve around 10,000 children each.’

Regarding typhoid, two vaccines have been WHO-prequalified in recent years, one of which, TyphiBev (Biological E), Cal was involved in inventing during his years in industry. These are glycoconjugate vaccines and differ from previous typhoid vaccines in that they can be given to infants (previous typhoid vaccines could not be given to children under two years) and were found to have excellent efficacy (over 80%) in post-licensure studies. Two further typhoid conjugate vaccines are likely to be licensed and prequalified in the next two years.

Cal’s team are currently very involved in supporting country decision-making around introduction of typhoid conjugate vaccines. To date, Pakistan, Zimbabwe and Liberia have been early adopters of these vaccines, with Nepal, Kenya and Malawi set to introduce typhoid vaccines in the coming months.

Alongside his Gates Foundation role, Cal is Professor of Vaccine Immunology and Senior Clinical Fellow at the University of Oxford’s Jenner Institute where the leads the Gonococcal Vaccine Project. This has adopted Native Outer Membrane Vesicle (NOMV) technology from his time in industry to develop a candidate vaccine against gonorrhoea. Again, there are no licensed vaccines against gonorrhoea and vaccine development has been a particular challenge as infection does not lead to protection. Effectively a vaccine has to do better than nature. Added to this is the growing threat of antimicrobial resistance among strains of gonococcus with the real threat of untreatable gonorrhoea.

Reflecting back on his academic and career journey, Cal talked about joining then-Green College in 1989 for his clinical studies having completed his pre-clinical at Keble College.

On his time at Green College, Cal remarked that after his pre-clinical studies ‘I was attracted to move to a smaller college, more focused on and with a mission more aligned to healthcare. I very much enjoyed my time at Green and still regularly meet up with my former tutor [Emeritus Fellow] Ken Fleming.

‘Green was incredibly supportive to me both as a clinical student and then during my DPhil.’

Rowing was also a big part of Cal’s time as a student in Oxford. He rowed three times in the Boat Race (1989, 1991, 1992). Cal remembers then-Warden Sir Crispin Tickell ‘sent a nice note about how he had to stop a meeting he was chairing to watch the Boat Race in 1992.’ During his DPhil, from 1992 to 1996, he was a member of the Olympic team, rowing in two World Championships and going as a reserve to the Atlanta Olympics. Those years were particularly hard work. Cal would train twice in the morning at Henley before travelling back to Oxford to start working in the lab. In the evening he would be training again, then return to the lab after dinner and often work till midnight.

Cal very much appreciated the support and good will of those at Green College during the years of combining studies with sport. ‘Ken Fleming was a key person, but plenty of other people looked out for me including [now Emeritus Fellows] Clive Hahn and Derek Jewell – who I knew as medical student and worked for as a junior doctor. It’s fantastic to be back in Oxford again as a Senior Clinical Fellow and I consider myself very fortunate.’ Cal also reconnected to Green Templeton College and is a current Common Room Member.

After his DPhil, Cal went on to work as a house officer with the Nuffield Department of Medicine at the John Radcliffe Hospital. It was during his time as a junior doctor that Cal became interested immunity to infection – and moved away from neurology to focus on immunology and infectious diseases.

After passing his MRCP exams, he went with his then-wife and six-week-old son to work in Kenya in a step towards broadening his horizons in relation to opportunities in global medicine. When he returned to the UK, after a couple of locum positions, Cal began training as a clinical immunologist in Birmingham, dividing his time between clinical work and laboratory research at the University of Birmingham.

Cal’s next step was to work in Malawi supported by a Wellcome fellowship, where he spent three-and-a-half years gaining insights into mechanisms of protective immunity against Salmonella. He returned to Birmingham to continue his investigations and publish his findings, alongside becoming a Consultant Immunologist.

Cal’s work on immunity to bacterial infections led to him being approached by industry to take up a new position leading the Exploratory Programme at the Novartis Vaccines Institute for Global Health in Siena, Italy. Here he was involved in developing new vaccines against a number of bacterial diseases, some of which are currently in clinical trials, as well as TyphiBev. At the same time as the invitation to move to industry, he was awarded a GSK fellowship which allowed him to keep his academic research going at Birmingham and maintain a position on the boundary of academia and industry. In the end, he spent four-and-a-half years in Italy. Though his Italian ‘was never brilliant’, Cal also continued to keep up his clinical work by seeing patients in the University Hospital in Siena.

By this time, he had students in his lab group working between industry and academia supported by European Commission FP7 funding. Novartis Vaccines was acquired by GSK in 2015 and Cal decided it was time to return to the UK where he began working back in Oxford at the Jenner Institute. Here he was awarded an MRC Senior Clinical Research Fellowship and began the Gonococcal Vaccine Project.

Cal has now been working at the Gates Foundation for five years. Although he has never relocated to their headquarters in Seattle, he was spending about a quarter of his time there pre-COVID, a quarter travelling elsewhere and the rest in Oxford where he runs his vaccine group at the Jenner Institute.

Separately, he directs BactiVac, the bacterial vaccines network which he established at the University of Birmingham in 2016 to accelerate the development of, and advocate for, vaccines against bacterial pathogens. Cal is excited to have seen this grow to over 1,200 members across 78 countries supported by the MRC and Department of Health and Social Care. The network has funded 50 catalyst projects to date, with 40 of these completed. In turn, these projects have attracted a further £15 million of follow-on funding.

In his spare time, Cal likes to keep active, running mountain marathons and competing in triathlons. Between him and his partner, Francesca Long, they have seven boys spread between sixth form and university who they enjoy spending time with.

Cal concluded our conversation optimistically, ‘It is an exciting time for global health and vaccines. The COVID pandemic obviously has had a very high cost in terms of health and mortality, as well as economic impact, but it has awakened the world to the importance of vaccines and human vulnerability to infectious diseases.’

‘We are now facing a silent pandemic caused by anti-microbial resistant bacteria and vaccines against these pathogens will become increasingly important. This is my focus. It brings together my experience in academia, industry and global health.’ And finally on making vaccines: ‘Academics in vaccinology have to link with industry as ultimately product development and licensed vaccines will always need manufacturers.’