On Nov. 3, Health Canada authorized the most recent bivalent vaccine to date, a Moderna booster, for those 18 and over designed to target multiple strains of the COVID-19 virus. It joins the Pfizer bivalent booster authorized on Oct. 1 for those 12 and over. The news comes as a relief to many as a July 2022 poll by the Angus Reid Institute shows that three of five vaccinated Canadians would get their next shot as soon as they were eligible. It may be natural to wonder whether they are safe, effective and what was their authorization based on.
What does it mean when a vaccine is bivalent?
But what exactly is a bivalent vaccine? Simply put, it is two vaccines combined in a single shot, a type of combination vaccine. This has the benefit of requiring fewer visits to a clinic/hospital, less stress for children, less time off work, fewer shots, fewer health-care resources used and more timely protection in a proven and safe manner.
There are two kinds of combination vaccines. Multitarget combination vaccines mix different vaccines that have been approved to address different “targets,” or diseases (e.g., MMR for measles, mumps and rubella; and DTaP for diphtheria, tetanus and pertussis). Both MMR and DTaP are so effective that vaccines for each of those individual diseases are simply no longer given in the U.S.
The other kind of combination vaccine is known as a multitype combination that is used when a particular pathogen (like COVID-19) has multiple “types,” or strains. Both authorized bivalent COVID boosters are multitype combination vaccines and target both the original strain as well as the Omicron BA.4/BA.5 variants.
Were these bivalent vaccines approved based on sufficient evidence?
There has been some concern about the trial size used to authorize these bivalent vaccines as well as worries that data is still being submitted on a rolling basis to Health Canada, which warrants some explanation.
Both the Moderna and Pfizer bivalent vaccines targeting BA.4/BA.5 were authorized based on sufficient safety evidence from previous clinical trials and immune response data based on BA.1 bivalent boosters. This is possible because both strains are part of the Omicron variety and are updated with relatively small tweaks.
A Moderna study compared 437 adults (18+) who took the Moderna BA.1 bivalent booster against 377 adults that received the original booster. The bivalent booster was found to be safe, effective and led to a stronger immune response compared to the previous booster. The results have been peer-reviewed by independent researchers and published in the New England Journal of Medicine. A clinical trial of a Pfizer bivalent vaccine that targets BA.1 included 610 individuals over 55 and had similar positive results. Another clinical trial found positive results for a booster that targeted the Omicron BA.1 strain alone in those between 18 and 55 years of age.
Higher antibody levels in both bivalent vaccines are a good sign.
While these sample sizes may seem small, it’s important to remember that this is quite common for vaccines that build upon safety data from previous strains. It builds upon the totality of previous evidence, existing technology and on already-approved formulas. The original Spikevax Moderna trials had more than 14,000 study participants while the Pfizer Comirnaty trials had more than 46,000 participants. Both have been administered to millions of people throughout the world and have been amply demonstrated to be safe and effective. Further clinical trials are still underway and both Pfizer and Moderna are required to submit data on a rolling basis to Health Canada.
How do they compare to previous vaccines and are they safe?
The Moderna bivalent booster performed better than the original Moderna monovalent booster, providing a similar or stronger immune response to the ancestral strain. More importantly, it led to a higher immune response to the Omicron BA.1 strain, but also against the more prevalent BA.4/BA.5 subvariants even though it wasn’t designed to target them specifically. These later subvariants are an offshoot of the Omicron lineage that still share some structural overlap. Such similarities can make existing bivalent boosters a good basis for developing boosters for future variants as well.
Clinical trials for the Pfizer bivalent booster have not been published. However, there is enough preclinical and clinical data to suggest that it will lead to a better immune response against the newer Omicron strains than the previous Pfizer booster. Data for the Pfizer bivalent booster for BA.4/BA.5 have been reviewed independently and recommended for safe use by Health Canada, the FDA in the U.S. and the European Medicines Agency, as was the Moderna BA.4/BA.5 bivalent booster.
Higher antibody levels in both bivalent vaccines are a good sign. It usually means a vaccine is better at fighting off infection and protecting against symptomatic disease. More studies are still needed to determine exactly just how much protection against severe disease and hospitalization these new bivalent boosters will provide compared to previous boosters.
Since both bivalent boosters approved by Health Canada are adapted versions of the original vaccines, their safety profiles and observed side effects are expected to be similar. No serious adverse events were observed, and safety data will continue to be collected on an ongoing basis. Side effects for both the Moderna and the Pfizer bivalent boosters are expected to be mild or at worst moderate and to resolve within a few days. The most likely symptoms are pain at the injection-site, in muscles and joints, as well as headaches.
Should you wait or get a bivalent booster as soon as possible?
Right now, NACI recommends a fall booster, with a preference for bivalent boosters, six months after a previous infection or vaccine but says that three months may be warranted in some cases if risks are higher. However, a longer interval between a booster dose and a prior dose/infection may lead to a more robust immune response.
Finally, it can be tempting to wait for an even newer updated booster or to feel like you have missed out if you got the original booster. However, variants and new vaccines will keep evolving and there is nothing wrong with using what we know works now. Previous non-bivalent boosters still provide protection against severe disease and hospitalization, even against the newer variants. Such data for the bivalent boosters is still being collected, but the immune response elicited by them is an encouraging sign.
If you haven’t gotten a booster in a while or if you are considered at-risk and cases are high in your area, consider getting boosted now. You can consult this decision tree designed to guide you depending on your situation. With temperatures dropping and the holiday season coming, we will all be spending more time indoors, which is expected to increase infections and hospitalization. Protect yourself and your loved ones by getting boosted to stay out of hospitals where other diseases can be picked up and to ease the strain on the health-care system.