Why is the protection time of the COVID-19 vaccine so short?

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Why is the protection time of the COVID-19 vaccine so short?

Why is the protection time of the COVID-19 vaccine so short?

Since the outbreak of the COVID-19 pandemic, hundreds of vaccines against SARS-CoV-2 have been developed worldwide.

Most of the vaccines that have been clinically used have shown satisfactory initial protection rates against the corresponding strains.

However, over time, the protection rates of the COVID-19 vaccines have rapidly declined, with almost all vaccines dropping to below 50% after 6 months.

In this hot research topic, the team led by Han Jiahui from the School of Life Sciences of Xiamen University analyzed relevant data and proposed that the rapid decline in the protection rate of COVID-19 vaccines is closely related to the nature of the virus itself.

The attributes of the novel coronavirus, such as being a non-systemic respiratory mucosal virus, high receptor affinity, short incubation period, and the high mutation rate resulting from large-scale infections, are the main reasons for the decline in vaccine protection rate.

They lead to a high antibody level threshold required to prevent COVID-19 infection, and the antibody levels produced by the COVID-19 vaccine will decrease below the required protective threshold in a relatively short period of time, thus losing their protective effect.

This report was published in the journal “Cellular & Molecular Immunology” under the title “COVID-19 vaccines and beyond.”

Why is the protection time of the COVID-19 vaccine so short?

Challenges posed by non-systemic respiratory viruses

Similar to the situation with COVID-19 vaccines, there are certain challenges in achieving ideal infection prevention effects with influenza vaccines and RSV vaccines, which were approved by the US FDA several months ago.

Experts in the field classify viruses such as influenza, RSV, and SARS-CoV-2 as non-systemic respiratory viruses because these viruses mainly replicate in the mucosa and nearby tissues, rarely depending on systemic dissemination.

One commonality of non-systemic respiratory viruses is their tendency to cause recurrent infections, which have never been effectively controlled by vaccines.

The development of next-generation SARS-CoV-2 vaccines needs to focus on enhancing secretory mucosal immunity and enhancing IgA responses, which has become a consensus in the field.

However, there is insufficient understanding of the immune response to such respiratory viruses, which limits the progress in devising new strategies for effectively controlling virus transmission.

High receptor affinity, short incubation period, and high mutation rate of COVID-19

A common saying is that the short-term protection period of SARS-CoV-2 vaccines is related to the rapid decrease in antibody levels after vaccination.

Comparatively, the HBV and HPV vaccines that can provide long-term protection, HBV’s serum antibody level decreases by half in about 60-100 days in the first 6 months, and HPV takes about 70-120 days, while SARS-CoV-2 takes about 40-90 days, there is no significant faster trend compared with HBV and HPV vaccines.

Therefore, the rapid decline in the protective effect of SARS-CoV-2 vaccines cannot be attributed to the rate of decrease in SARS-CoV-2 antibodies exceeding that of other vaccines.

The high receptor affinity of SARS-CoV-2 poses a challenge to the protective effect of vaccines. The receptor affinity of SARS-CoV-2 is 3-40 nM, higher than that of HBV (67.1 nM), measles (80-400 nM), and poliovirus (110-670 nM), which have persistent vaccine efficacy.

The higher the affinity between the virus and the receptor, the more difficult it is for neutralizing antibodies to effectively prevent the virus from binding to host cells.

Differences in the incubation period may also lead to differences in the effectiveness of vaccines against different viruses.

The incubation period of SARS-CoV-2 is about 2-10 days. The flu virus is about 1-3 days, measles virus is about 9-14 days, hepatitis B virus is about 50-150 days, and HPV is about 50-150 days.

Vaccination to produce serum antibodies can neutralize the virus before it develops, and a short incubation period is not conducive to antibody prevention of infection.

In addition, a short incubation period may prevent the vaccine’s memory response from keeping up with the virus’s development.

The continuous mutation of SARS-CoV-2 strains is one of the important reasons for the decrease in the protective effect of vaccines and the reinfection of the virus.

Because antibodies produced against previous virus strains may not effectively bind to newly emerging mutated antigenic sites, the actual neutralizing antibody titer decreases rapidly.

With the emergence of the Omicron variant, this effect is particularly pronounced.

After vaccination, the neutralizing antibody titer against Omicron is 1/10 of that against the Delta variant.

While the vaccine provides about 90% protection against the Delta strain, the protection rate against Omicron is only about 50%.

High antibody protection threshold of COVID-19

There is a correlation between serum antibody levels and protective efficacy, and maintaining neutralizing antibody titers above a threshold is a necessary condition for effective protection.

The protective threshold level for HBV infection is usually 10 mIU/mL, and after complete vaccination, the antibody level exceeds this threshold by hundreds of times.

The antibody protective threshold for measles is considered to be 120 mIU/mL, and the vaccine increases the antibody level to about 1000 mIU/mL.

The neutralizing antibody titer for protection against poliovirus infection is about 1:4-8, and the vaccine can increase the neutralizing antibody titer to about 1:400-5000.

For SARS-CoV-2, the serum antibody levels of individuals infected or vaccinated are about 1:200-1000, and it is currently only known that the neutralizing antibody titer corresponding to a 50% protection rate against SARS-CoV-2 is between 1:10-40, and its protective threshold should be higher than this level.

These data indicate that the initial antibody titer far above the threshold is associated with long-term protection, and the protective threshold for SARS-CoV-2 infection is relatively high.

Reasons for the reduced risk of COVID-19

Mutant strains of SARS-CoV-2, especially Omicron, have significantly reduced virulence, and the spike protein of Omicron has less dependence on TMPRSS2 (transmembrane protease serine 2).

Since TMPRSS2 is highly expressed in the lungs, while the expression of ACE2 from the upper respiratory tract to the lungs gradually decreases, Omicron tends to infect or spread in the upper respiratory tract rather than the lungs.

Since tissue damage in the respiratory tract usually does not endanger life, while lung damage may pose a lethal risk, the lower risk of Omicron is likely due to the limited extent of its attack on the lungs.

Conclusion

This report compares various viruses and vaccines to show that the inability of current COVID-19 vaccines to provide long-term protection is due to the nature of the virus, not the rate of decline in SARS-CoV-2 antibodies.

The rapid mutation of SARS-CoV-2 caused by large-scale infections worldwide, its high affinity for host cells, and its short incubation period are the main reasons why vaccines are not as effective (Figure 1A).

Although the long-term protective effect of COVID-19 vaccines is limited, they have significantly reduced the risk of death and made important contributions to controlling the COVID-19 pandemic.

However, vigilance must be maintained, as if future mutations lead to a shift in the site of infection back to the lungs, the danger may reappear (Figure 1B).

In order to prevent SARS-CoV-2 in the long term and deal with similar unknown viruses, new immune strategies must be developed to induce more effective immune responses than current methods.

Original article link: Nature.com