Virus World

BACKGROUND

Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection.

METHODS

In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein–based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated.

RESULTS

A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR–confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups.

CONCLUSIONS

A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596. opens in new tab.)

Published in NEJM (Feb. 16, 2023):

https://doi.org/10.1056/NEJMoa2209604 

One ingredient used in some COVID-19 vaccine candidates is squalene, a natural oil made in the liver of sharks. Squalene is currently used as an adjuvant in medicine - an ingredient that increases the effectiveness of a vaccine by creating a stronger immune response. British pharmaceutical company GlaxoSmithKline currently uses shark squalene in flu vaccines. The company said it would manufacture a billion doses of this adjuvant for potential use in coronavirus vaccines in May. Around 3,000 sharks are needed to extract one tonne of squalene.

Shark Allies, a California-based group, suggests that if the world's population received one dose of a COVID-19 vaccine containing the liver oil, around 250,000 sharks would need to be slaughtered, depending on the amount of squalene used. If two doses are needed to immunise the global population, which is likely according to researchers, this would increase to half a million. To avoid threatening shark populations, scientists are testing an alternative to squalene - a synthetic version made from fermented sugar cane. Stefanie Brendl, founder and executive director of Shark Allies, said: "Harvesting something from a wild animal is never going to be sustainable, especially if it's a top predator that doesn't reproduce in huge numbers. "There's so many unknowns of how big and how long this pandemic might go on, and then how many versions of it we have to go through, that if we continue using sharks, the numbers of sharks taken for this product could be really high, year after year after year."

According to estimates made by conservationists, around three million sharks are killed every year for squalene, which is also used in cosmetics and machine oil. There are fears that a sudden rise in demand for the liver oil could threaten populations and see more species become endangered as many species rich in squalene, such as the gulper shark, are already vulnerable.