UCLA researchers in the Department of Medicine have utilized a highly attenuated replicating bacterial vector platform to develop a vaccine against SARS-CoV-2 in humans and animals to prevent COVID-19.
BACKGROUND:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), closely related to SARS-CoV, is an enveloped, single-stranded positive RNA virus. Starting in the final months of 2019, the virus caused an ongoing pandemic of COVID-19 that quickly spread worldwide with millions of confirmed cases and hundreds of thousands of deaths. There are currently no licensed vaccines against COVID-19 resulting in an urgent need for a safe and potent vaccine.
INNOVATION:
UCLA researchers led by Dr. Marcus Horwitz have utilized a highly attenuated replicating bacterial vector platform to develop a vaccine for preventing the disease COVID-19 caused by SARS-CoV-2 in humans and animals. The replicating bacterial vector (LVS ΔcapB) was derived from Live Vaccine Strain (LVS), a vaccine against tularemia itself derived from a relatively low virulence tularemia species and administered to as many as 60 million people. LVS ΔcapB is >10,000 fold less virulent but retains the ability to induce a highly potent immune response. Recently completed human trials of a newly manufactured version of LVS have demonstrated a reasonable safety profile of this double-deletional parent. Previous use of the LVS ΔcapB vector to express antigens of target pathogens has generated exceptionally potent vaccines that protect against death after lethal respiratory challenge in highly sensitive animal models. The researchers showed that the administration of these vaccines induces balanced immunogenicity with both B cell responses, including the generation of neutralizing antibody, and T cell responses (Th1 type with CD4 and CD8 T cells). Current research efforts are focusing on challenge animal studies against SARS-CoV-2.
POTENTIAL APPLICATIONS:
- Vaccine for SARS-CoV-2
ADVANTAGES:
- Excellent safety profile 10,000 less virulent than the parent vector in a mouse model
- Balanced immunogenicity
- Ease of administration
- Low manufacturing costs with no need for purification as with viral vectors
- Ease of rapid large-scale manufacture
- No animal products needed
- No need for adjuvant
- No pre-existing immunity
- Ease of modification in response to mutated virus
- Simplified regulatory approval
- Concurrent administration with other vaccines using the same vector
DEVELOPMENT-TO-DATE:
Nine COVID-19 vaccines have been constructed and demonstrated to express the relevant SARS-CoV-2 proteins singly and in combination. An animal challenge study against SARS-CoV-2 is underway.