How effective is the live attenuated SARS-CoV-2 vaccine?

In a recent review published in PLoS pathogenresearchers commented on the use of a live-attenuated whole-virus vaccine (LAV) as a coronavirus disease 2019 (COVID-19) vaccine.

Background

The COVID-19 pandemic has caused significant mortality and morbidity worldwide and has led to the development of effective therapeutic vaccines and drugs to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Is required.Several COVID-19 vaccines have been administered and have demonstrated anti-SARS-CoV-2 Effectivenesshowever, the continued emergence of SARS-CoV-2 variants (VOCs) of concern threatens vaccine efficacy.

Current vaccines are based on rapid vaccine platforms such as messenger ribonucleic acid (mRNA), adenoviral vectors, deoxyribonucleic acid (DNA) vectors, inactivated and protein subunit vaccines. Vaccine platforms with long development times and pathways have been largely overlooked in the face of rapidly emerging VOCs.

New vaccines are needed to induce long-term and broad-based immune protection against current and yet-to-be-emerged SARS-CoV-2 VOCs. An intranasal (in) single-dose LAV vaccine, being developed by Codagenix and the Serum Institute of India, has completed Phase I clinical trials with promising immunogenicity and safety.

In the current study, researchers reviewed the LAV vaccine and its efficacy against SARS-CoV-2.

Application and immunogenicity of LAV vaccine

Most of the vaccines licensed to prevent viral infections are LAV vaccines. It has been used for decades to provide long-term immunity against several viruses, including herpes zoster virus (HZV), polio virus, and yellow fever virus. The smallpox vaccine is effective and based on the vaccinia virus (the LAV virus closely related to the smallpox virus).Other LAVs routinely used include mumps, measles, rubella, rotavirus, and chicken pox.

Current COVID-19 vaccines (such as BNT162b2) are administered intramuscularly (im), with the injection site distant from the site of infection. As a result, strong immunoglobulin G (IgG) responses and robust systemic immunity are generated, but mucosal immunity is poor. Furthermore, im injection did not generate tissue-resident B and T lymphocytes, viral shedding It can occur after vaccination and causes breakthrough infection of SARS-CoV-2. Moreover, immune responses induced by vaccination are not as strong as those induced by natural infection and decay rapidly.

In contrast, the LAV vaccine is administered intranasally to the site of SARS-CoV-2 entry and produces strong IgG and IgA titers with strong systemic and local (mucosal) immunity. In addition, potent tissue-resident lymphocytes (memory B and T lymphocytes) are generated within the pathway, resulting in less viral shedding and reduced risk of breakthrough infection.

Importantly, LAV mimics natural infection and confer robust and durable immunity comparable to that induced by natural infection. Moreover, in-route is potentially faster, simpler and more cost-effective than currently administered vaccines, making it highly desirable for broad and rapid global vaccination coverage. sc) route. This is a delivery route that can effectively induce systemic immune responses and broadly and comprehensively enhance immunity after primary vaccination.

Efficacy of LAV vaccine against SARS-CoV-2

Vaccines that induce immune responses only against one SARS-CoV-2 structural protein, usually the spike (S) protein, induce narrower responses than vaccines that induce immunity against live virus. Emerging S variants therefore do not contain additional SARS-CoV-2 epitopes and may not induce broad cross-reactive immunity against continuously emerging SARS-CoV-2 variants. , may easily evade targeted vaccine-induced immune responses. Therefore, current vaccines may need constant updating and modification based on the evolution of SARS-CoV-2.

The LAV vaccine induces a broad and cross-reactive immune response by inducing T-lymphocyte and B-lymphocyte epitopes of all SARS-CoV-2 proteins and targets conserved regions of SARS-CoV-2. It is effective and the efficacy of LAV vaccines is subject to viral changes. In particular, the LAV vaccine induces a strong CD8+ (differentiation cluster 8+) T lymphocyte response and strong tissue-resident memory T lymphocytes (T_RM).

Conclusion

In conclusion, based on the results of our review, immune responses to SARS-CoV-2 can be induced by natural infection or vaccination. Currently used SARS-CoV-2 S-targeted and intramuscular mRNA COVID-19 vaccines are effective against the virus but less effective against the highly immune evasive and highly contagious omicron variant is shown. Furthermore, it has been reported that immunity from mRNA vaccination is lower than that from natural infection and declines rapidly.

In contrast, the intranasally administered LAV vaccine, which targets the whole virus, can confer broad, cross-protective and long-lasting immunity against SARS-CoV-2, allowing new SARS-CoV Less likely to be affected by -2 mutants. LAV vaccines have the potential to induce local and systemic immune responses and thus can effectively enhance the immunity conferred by primary vaccination. However, the LAV vaccine is not recommended for immunocompromised individuals.