PRESIDENT BIDEN GOT HIS BIVALENT COVID-19 BOOSTER
Authors: Katharine Olson and Wenhui Mao
Vaccines have played a large role in the global COVID-19 response and saved numerous lives. However, when highly transmissible variants such as Omicron (BA.1) appeared and quickly dominated the reported cases, the effectiveness of vaccinations was noticeably waning. The first U.S. case of BA.1 was reported December 1st, 2021, and by January 8th, 2022 it comprised 95% of new cases. In the last week of January 2022, confirmed new cases worldwide hit 23 million which is in stark contrast to previous highs of 5 million new cases a week. At the start of the BA.1 wave in late 2021, the primary vaccination series was only 44% effective at preventing infection and hospitalization. This prompted the push globally to administer booster vaccine doses as three doses were found to be 71.6% effective against BA.1. Waning effectiveness led vaccine manufacturers to create bivalent vaccines that could target two COVID-19 strains and provide better protection.
PRESIDENT In this blog, we describe the features of the available bivalent COVID-19 vaccines, track the regulatory approval and the procurement of bivalent COVID-19 vaccines, new vaccine technologies in clinical development, and implications of introducing these medical countermeasures.
Mechanism and efficacy of the bivalent COVID-19 vaccines
Bivalent vaccines are one of the newest tools to protect against COVID-19 infection and severe outcomes. Bivalent COVID-19 vaccines contain a portion of the spike protein from the original wild-type strain as well as a portion of the omicron spike protein. Both Moderna (Spikevax) and Pfizer (Comirnaty) have updated their existing monovalent mRNA vaccines to include an omicron component, whether that be a portion of the original BA.1 or subvariant BA.4/5 spike protein.
Early clinical trials indicated that administration of a bivalent booster dose increased the average titer of neutralizing antibodies to BA.1 by 1.6 times that of a monovalent booster in those with no prior COVID-19 infection. In addition, administration of a bivalent booster dose increased neutralizing antibodies to BA.4/5 by 1.5 times that of a monovalent booster. While statistically significant differences in antibody titers have been found, there is concern that this might not translate to clinical significance.
Bivalent vaccines are meant to be administered as booster doses after the completion of the primary vaccination series and are recommended to be prioritized for high-risk populations. Similar to how the influenza vaccines work, the idea is that as the circulating COVID-19 strain changes, the boosters can be updated to provide targeted protection. These bivalent COVID-19 vaccines come in advance of a predicted surge in cases this fall and winter in the northern hemisphere, providing an extra line of defense for those who need it most.
Regulatory approval and procurement of bivalent COVID-19 vaccines
Currently, the bivalent vaccines from Pfizer and Moderna have received provisional approval in only a handful of high-income countries (HICs) or regions: European Commission, Italy, USA, UK, Israel, Canada, Australia, Taiwan, South Korea, and Japan. While the BA.4/5 subvariant has replaced BA.1 as the widely circulating strain, several countries have opted to prioritize purchasing vaccines that contain the BA.1 protein. Only the United States and Israel have purchased BA.4/5 bivalent vaccines. The discontinuity in approval of these vaccines globally coupled with the lack of clear clinical efficacy may create “two tiers” of vaccines, making it harder to achieve high levels of booster coverage and fueling vaccine hesitancy.
Purchases of these bivalent COVID-19 vaccines have come from COVAX and high-income entities which have achieved high levels of primary vaccination coverage, and are now focused on getting booster shots to vulnerable populations. There is significant vaccine supply available and wealthy countries have purchased far more doses than needed to vaccinate priority populations. Australia has purchased 15 million bivalent doses, enough to vaccinate the age 65+ population 3.5 times and the healthcare worker population 8.4 times. The United States has purchased nearly 171 million doses of bivalent vaccines which is over 3 times as many doses needed to vaccinate its 65+ and healthcare worker populations. In contrast to WHO recommendations that booster doses should be prioritized amongst high-risk populations, the United States is encouraging all age groups to take the bivalent vaccine, which may in part explain the disparity in doses purchased. Canada has purchased 12 million doses, which could vaccinate the 65+ population 1.7 times and the healthcare worker population 4.6 times.