The authorization for the COVID-19 bivalent vaccine was formally withdrawn by the U.S. Food and Drug Administration (FDA) as a planned regulatory action. This change was not due to new safety concerns but was driven by the continuous, rapid evolution of the SARS-CoV-2 virus. The decision was a science-based measure to ensure the public received the best possible protection against circulating variants. The withdrawal made way for a newer formulation that was a more precise match for the current viral threat, streamlining the national vaccination strategy.
Understanding the Original Bivalent Formulation
The bivalent vaccine, introduced in late 2022, represented an important step in adapting vaccine technology to a changing virus. It was designed to teach the immune system to recognize two distinct spike protein sequences simultaneously. The formulation contained messenger RNA (mRNA) components targeting the spike protein of the original SARS-CoV-2 strain (the ancestral or Wuhan-Hu-1 strain).
The second component targeted the spike protein shared by the Omicron BA.4 and BA.5 subvariants, which were dominant when the vaccine was authorized. This dual-component approach was intended to broaden the immune response and enhance immunity against the circulating Omicron lineage. The goal was to improve neutralizing antibody levels against these new variants, which demonstrated significant immune evasion.
Viral Evolution and Waning Relevance
The primary reason for the bivalent vaccine’s withdrawal was the relentless evolution of SARS-CoV-2, which outpaced the vaccine’s design. The virus’s genetic material mutates constantly, leading to new variants that are antigenically distinct from their predecessors. By late 2022 and early 2023, the Omicron BA.4/BA.5 subvariants, which the bivalent shot was designed to target, had been replaced by the genetically distant XBB lineage.
This rapid shift in variant dominance meant the bivalent formulation was no longer the optimal immunological match for the circulating strains. Scientific data demonstrated that the presence of the original, ancestral strain component in the bivalent vaccine was no longer beneficial. Including the ancestral component was thought to contribute to a phenomenon known as “immune imprinting,” where the immune system preferentially recalls its first response, potentially limiting the magnitude of the response against the newer variant component. The FDA and the Centers for Disease Control and Prevention (CDC) concluded that retaining this older component was hindering, rather than helping, the immune system’s ability to generate a robust defense against the new XBB strains.
A targeted approach would yield a stronger, more relevant immune response against the current viral threat. Removing the outdated components was a strategic move to focus the immune system’s resources on developing antibodies specific to the XBB lineage. The formulation had lost its relevance as the virus continued to drift farther away from the strains it was designed to combat. Therefore, the authorization was rescinded because the bivalent shot no longer offered the maximum possible protection against the strains causing the majority of infections.
The Shift to the Updated Monovalent Vaccine
The bivalent vaccine was replaced by an updated monovalent formula, which exclusively targets a specific spike protein from the XBB lineage. This new formulation, which became the standard for the 2023–2024 season, was chosen to target the Omicron subvariant XBB.1.5. Regulators selected XBB.1.5 because it was broadly representative of the variants circulating at the time and was shown to elicit an immune response effective against other emerging XBB sublineages.
The transition to a monovalent vaccine simplifies the immunization strategy, moving away from the complex dual-strain approach. This simplification is rooted in the goal of maximizing the immune system’s focus on the most common circulating strain. Clinical and non-clinical data supported that a single component, more closely matched to the current virus, would generate higher levels of neutralizing antibodies against the actual threats faced by the population. This updated shot is not considered a traditional “booster” for the original vaccine series but rather an updated primary vaccine designed to match the current year’s dominant strains, similar to the annual flu shot.
Current Recommendations for Vaccination
With the bivalent vaccine no longer authorized, the updated monovalent vaccine is now the standard of care for all eligible individuals. The CDC recommends that everyone aged six months and older receive a dose of the updated formula, regardless of their previous vaccination history. Individuals who previously received the bivalent shot should still receive the updated monovalent vaccine to ensure protection against currently circulating strains.
The updated monovalent vaccine, which targets the XBB.1.5 subvariant, provides the best available defense against severe illness, hospitalization, and death. For most people aged five years and older, a single dose of the updated vaccine is recommended. Individuals who recently had a COVID-19 infection may consider delaying their vaccine by about three months, though the updated shot is still advised to ensure a robust response.