A universal COVID vaccine represents a scientific undertaking to develop a single immunization that offers broad, long-lasting protection against various SARS-CoV-2 variants and other related coronaviruses. Such a vaccine holds significant promise in the continuing effort to control COVID-19 and prepare for future viral threats.
Limitations of Current COVID-19 Vaccines
Existing COVID-19 vaccines primarily target the spike protein of the initial SARS-CoV-2 strain. This focus means their effectiveness can decrease against new variants with mutations in this protein, leading to reduced protection over time. For instance, the effectiveness of a bivalent mRNA vaccine against hospitalization declined from 62% at about 33 days to 24% at 150 days. This decline necessitates frequent booster shots or updated vaccine formulations to maintain protection against circulating variants.
The continuous emergence of new variants, such as Omicron subvariants, requires ongoing vaccine updates, similar to the seasonal flu shot. The rapid mutation rate of the virus can mean that by the time updated boosters are developed and distributed, a different variant may already be prevalent. This cycle of adaptation also presents challenges for global vaccine distribution and uptake, as variant-specific approaches complicate logistics and lead to inequities in access, especially in low- and middle-income countries.
Designing a Universal COVID Vaccine
The design of a universal COVID vaccine centers on targeting “conserved regions” of the virus, which are parts that mutate infrequently across different variants. One approach involves developing pan-sarbecovirus vaccines, designed to protect against a broader family of coronaviruses, including SARS-CoV-2, SARS-CoV-1, and MERS-CoV, as well as future variants. These vaccines aim to elicit a robust immune response by focusing on antigens shared across various sarbecoviruses.
Another strategy involves stimulating T-cell immunity, going beyond antibody-focused responses. T cells can recognize a wider range of viral epitopes, including those in highly conserved regions like ORF1ab, which are less affected by mutations in the spike protein. This T-cell focused approach could provide protection against severe disease and death, even if new variants emerge that evade antibody responses. Researchers are also exploring mosaic vaccines or nanoparticle platforms that present multiple viral antigens simultaneously. These platforms can arrange fragments from various strains on a nanoparticle scaffold, allowing the immune system to identify commonalities and generate broadly reactive antibodies and T-cell responses.
Advancements in Universal Vaccine Research
Research into universal COVID vaccines is ongoing, with various institutions and companies exploring different vaccine platforms. The National Institute of Allergy and Infectious Diseases (NIAID) is actively funding multidisciplinary teams to develop pan-coronavirus vaccine candidates. These efforts incorporate insights into coronavirus virology and immunology, along with innovative vaccine and adjuvant technologies.
mRNA technology has shown promise in creating multi-epitope vaccines that target conserved T-cell and B-cell epitopes. Protein subunit and viral vector platforms are also being explored. For example, the Walter Reed Army Institute of Research (WRAIR) developed a spike ferritin-based nanoparticle (SpFN) vaccine, which entered Phase I clinical trials in April 2021. Additionally, the U.S. Department of Health and Human Services (HHS) and the National Institutes of Health (NIH) have launched the “Generation Gold Standard” initiative, focusing on a beta-propiolactone (BPL)-inactivated, whole-virus platform to induce broad B and T cell immune responses against multiple strains of pandemic-prone viruses.
The Broader Public Health Impact
A successful universal COVID vaccine could significantly simplify vaccination campaigns by reducing the need for frequent updates and booster shots, which currently complicate logistics and public adherence. This long-lasting, broad protection would reduce the burden on disease surveillance systems, as the focus could shift from tracking specific variants to a more generalized preparedness. Such a vaccine would also enhance global pandemic preparedness by offering a foundational defense against future coronavirus threats, including those that might emerge from animal populations.
A universal vaccine could foster greater health equity by providing more stable and accessible protection worldwide, particularly in low- and middle-income countries that often face challenges with vaccine distribution and access. This would reduce the disparities in vaccination rates observed during the pandemic, where high-income countries initially led in vaccination efforts while low-income countries lagged behind. Ultimately, a universal vaccine could contribute to achieving long-term control over SARS-CoV-2 and strengthen global health security against emerging infectious diseases.