Medical Bulletin 18/ September/ 2024 - Video

The World Health Organization (WHO) has announced the MVA-BN vaccine as the first vaccine against mpox to be added to its prequalification list.

“This first prequalification of a vaccine against mpox is an important step in our fight against the disease, both in the context of the current outbreaks in Africa, and in future,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “We now need urgent scale up in procurement, donations and rollout to ensure equitable access to vaccines where they are needed most, alongside other public health tools, to prevent infections, stop transmission and save lives.”

The MVA-BN vaccine can be administered in people over 18-years of age as a 2-dose injection given 4 weeks apart. After prior cold storage, the vaccine can be kept at 2–8°C for up to 8 weeks.

“The WHO prequalification of the MVA-BN vaccine will help accelerate ongoing procurement of the mpox vaccines by governments and international agencies such as Gavi and Unicef to help communities on the frontlines of the ongoing emergency in Africa and beyond,” said Dr Yukiko Nakatani, WHO Assistant Director-General for Access to Medicines and Health Products. “The decision can also help national regulatory authorities to fast-track approvals, ultimately increasing access to quality-assured mpox vaccine products.”

The WHO Strategic Advisory Group of Experts (SAGE) on Immunization reviewed all available evidence and recommended the use of MVA-BN vaccine in the context of an mpox outbreak for persons at high risk of exposure. While MVA-BN is currently not licensed for persons under 18 years of age, this vaccine may be used “off-label” in infants, children and adolescents, and in pregnant and immunocompromised people. This means vaccine use is recommended in outbreak settings where the benefits of vaccination outweigh the potential risks.

WHO also recommends single-dose use in supply-constrained outbreak situations. WHO emphasizes the need to collect further data on vaccine safety and effectiveness in these circumstances.

Available data shows that a single-dose MVA-BN vaccine given before exposure has an estimated 76% effectiveness in protecting people against mpox(5), with the 2-dose schedule achieving an estimated 82% effectiveness. Vaccination after exposure is less effective than pre-exposure vaccination.

Good safety profile and vaccine performance has been consistently demonstrated in clinical studies, as well as in real-world use during the ongoing global outbreak since 2022. In light of the changing epidemiology and emergence of new virus strains, it remains important to collect as much data as possible on vaccine safety and effectiveness in different contexts.

Reference: WHO News “WHO prequalifies the first vaccine against mpox” https://www.who.int/news/item/13-09-2024-who-prequalifies-the-first-vaccine-against-mpox

New evidence shows that extended estrogen suppression treatment using aromatase inhibitors for hormone receptor-positive postmenopausal breast cancer is safe; it does not increase the risk of coronary artery calcification, a sign of active coronary atherosclerosis, as some prior studies had indicated.

An article in the Canadian Journal of Cardiology, details the findings from a retrospective, cross-sectional observational study that investigated the association between the duration of aromatase inhibitor treatment and the severity of coronary artery calcification in postoperative breast cancer patients.

Lead investigator Yu Hiasa, MD, Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine, Toon, Japan, explains, “Although there is an ongoing discussion on the optimal duration of aromatase inhibitor therapy (5 years or 10 years), our data suggest that longer aromatase inhibitor use (as often used to prevent or suppress late recurrences or spread of breast cancer) is safe, at least in regard to coronary artery calcification.”

The investigators conducted a single-center, retrospective, cross-sectional observational study among 357 postmenopausal breast cancer patients who initiated adjuvant endocrine therapy with aromatase inhibitors for breast cancer between August 2010 and October 2022 as outpatients. Coronary artery calcification was quantified using a visual ordinal scoring system, and patient characteristics were assessed based on the presence of coronary artery calcification. Independent risk factors for elevated coronary artery calcification scores were identified through a multivariable logistic regression model.

Co-investigator Akinori Higaki, MD, PhD, Department of Cardiology, Pulmonology, Hypertension & Nephrology, Ehime University Graduate School of Medicine, Toon, Japan, adds, "Our analysis of the postoperative breast cancer patient cohort revealed that the duration of treatment with aromatase inhibitors and the presence of osteoporosis were not associated with coronary artery calcification."

Reference: Impact of Aromatase Inhibitors Treatment Duration on Coronary Artery Calcification in Postoperative Patients with Breast Cancer, Canadian Journal of Cardiology (2024). DOI: 10.1016/j.cjca.2024.05.012

Monoclonal antibodies -- treatments developed by cloning a cell that makes an antibody -- could help provide an answer to the growing problem of antimicrobial resistance, say scientists.

A team led by researchers at the University of Cambridge has developed a monoclonal antibody drug, using a technique involving genetically engineered mice, that may help prevent infection from Acinetobacter baumannii, a bacteria associated with hospital-acquired infections, which is particularly common in Asia.

Professor Stephen Baker from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge said "A. baumannii is good at sticking to medical equipment, and if people are vulnerable or don't have a particularly well-developed immune system, they can succumb to this infection and get aggressive pneumonia requiring ventilation -- and in many cases, the patients can acquire the infection from the ventilation itself.

"The bacteria are naturally resistant to many antimicrobials, but as they're now found in hospitals, they've acquired resistance to almost everything we can use. In some hospitals in Asia, where the infections are most common, there isn't a single antibiotic that will work against them. They've become impossible to treat."

In a study published today in Nature Communications, the team produced monoclonal antibodies using transgenic mice -- mice that have been genetically-engineered to have a human-like immune system, producing human antibodies instead of mouse antibodies. They went on to show that these monoclonal antibodies were able prevent infection with A. baumannii derived from clinical samples.

Monoclonal antibodies are a growing area of medicine, commonly used to treat conditions including cancer (for example, Herceptin for treating some breast cancers) and autoimmune disease (for example, Humira for treating rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis).

Usually, monoclonal antibodies are developed from the antibodies of patients who have recovered from an infection, or they are designed to recognise and target a particular antigen. For example, monoclonal antibodies targeting the 'spike protein' of the SARS-CoV-2 coronavirus were explored as a way of treating COVID-19.

In the approach taken by the Cambridge team, however, transgenic mice were exposed to the outer membrane of A. baumannii bacteria, triggering an immune response. The researchers then isolated almost 300 different antibodies and tested which of these was the most effective at recognising live bacteria, identifying the single monoclonal antibody mAb1416 as the best.

Reference: Stephen Baker, Aishwarya Krishna, Sophie Higham, Plamena Naydenova, Siobhan O’Leary, Josefin Bartholdson Scott, Katherine Harcourt, Sally Forrest, David Goulding, To Nguyen Thi Nguyen, Nguyen Duc Toan, Elizaveta Alekseeva, Qingqing Zhou, Ilaria Andreozzi, Barbara Sobotic, Hannah Craig, Vivian Wong, Nichola Forrest-Owen, Dana Moreno Sanchez, Claire Pearce, Leah Roberts, Simon Watson, Simon Clare, Mili Estee Torok, Gordon Dougan, Paul Kellam, John S. Tregoning, Stephen T. Reece. Exploiting human immune repertoire transgenic mice for protective monoclonal antibodies against antimicrobial resistant Acinetobacter baumannii. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-52357-8