Sub-Journal of "Cell": The new coronavirus can evade antibodies in the nose!

Has everyone been vaccinated against the new crown? There are now more than 100 million people vaccinated against the new crown in the world, and there are more than 30 million in China.
Although they are vaccinated, experts still recommend that you wear masks at ordinary times.
Many people may not understand it.
Research led by researchers at the Academy may be able to explain the experts’ concerns.

 The researchers used the golden hamster model to simulate the infection of the new crown virus after different methods of inoculation with the new crown antibody or vaccine.

They found that after vaccination, lung infections and damage were indeed significantly reduced, but infections in the nasal cavity did not decrease.
Researchers believe that this will have a significant impact on reinfection and vaccines.

The results of the study were published in the journal "Cell·Host & Microorganism" [1].

Group photo of the research team This study used a total of 3 neutralizing antibodies and 1 vaccine.

The researchers first obtained 4 neutralizing antibodies from peripheral blood mononuclear cells provided by 12 patients with new crown infections during the recovery period.
Among them, ZDY28, ZDY49 and ZDY95 are more similar, and the immunoglobulin heavy chain variable region gene of ZDY20 3 and immunoglobulin κ chain variable region gene 1, which are different from them, may have higher antiviral activity [2,3].

 Among the four antibodies, ZDY28, ZDY49, and ZDY95 have similar binding ability to the new coronavirus, which is lower than ZDY20, and the neutralizing activity of ZDY20 is higher than the first three.

Therefore, the researchers retained ZDY20 as a neutralizing antibody for subsequent experiments.

 They vaccinated golden hamsters with ZDY20 preventively, and then infected the hamsters with the new coronavirus.
They found that similar to the results of previous studies [4], the hamsters basically recovered quickly, and the virus was cleared within 1 week after infection.

 On the 4th day after nasal infection with the new coronavirus, the turbinates, trachea and lung tissues of the hamsters inoculated with HIV-1 specific antibodies in the control group were easily detected for infection, while the hamsters inoculated with a low dose (5mg/kg) of ZDY20 In the three sites, 100%, 33% and 67% were detected with infection.
High-dose (10mg/kg) ZDY20 had the best effect, and only 25%, 25% and 50% were detected with infection respectively.

 Quantitative testing showed that the virus levels in the lungs were reduced by three logarithmic units on average, but the virus levels in the turbinates and trachea were not significantly reduced.

 Pathological analysis also showed that compared with the control group, inoculation with ZDY20 significantly reduced lung tissue damage in hamsters, especially in the high-dose group, with only mild interstitial alveolar inflammation and less septal infiltration and congestion, as observed in lung slices Very few viral nucleocapsid proteins were expressed, and the virus infection in the turbinate tissues of the three groups of hamsters did not differ much.

Comparison of lung tissue damage staining (H&E) and nucleocapsid protein immunofluorescence staining (IF) of hamsters at high and low doses of ZDY20 and the control group (from top to bottom) These results indicate that preventive vaccination with ZDY20 can inhibit viral infections in the lungs , But the effect of preventing upper respiratory tract infection is not good.

 Could it be that ZDY20 itself is not strong enough? To verify this, the researchers tested two other neutralizing antibodies (ZB8 and 2-15), and their half-inhibitory concentration (IC50) can reach up to 500 times that of ZDY20.

 In subsequent experiments, whether it was intraperitoneal injection (4.
5 mg/kg ZB8 and 1.
5 mg/kg 2-15) or intranasal inoculation (10 mg/kg ZDY20 and 4.
5 mg/kg ZB8), only lungs were observed Viral infection in the lower part of the body has been reduced, and there is still no significant difference in the infection in the turbinate.

 The same result also occurred in hamsters vaccinated with DNA.

 Based on this, the researchers concluded that passive immunization and muscle DNA vaccine injections are unlikely to effectively protect the tissues in the turbinate from the powerful new coronavirus infection.

Image from: Pixabay.
com The co-corresponding author of this study, Yuan Guoyong, Chair Professor of Infectious Diseases, Department of Microbiology, University of Hong Kong School of Medicine, said that although after vaccination or antibody treatment, there will indeed be high titers of neutralizing antibodies in the serum.
However, this does not completely guarantee that the upper respiratory tract is protected from the new coronavirus infection.

The public needs to be aware of this and remember that after vaccination, they still need to maintain the habit of wearing masks and washing hands frequently to effectively prevent the spread of the virus [5].

 Chen Zhiwei, a professor in the Department of Microbiology at the University of Hong Kong School of Medicine who led this research, raised the question from another perspective.
At present, for asymptomatic infections, the effectiveness of vaccination is not satisfactory.
This research not only explains the inability to completely prevent asymptomatic infections.
The principle also reveals the importance of developing vaccines against the nasal mucosa [5].

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 References: [1] Zhou D, Chan JFW, Zhou B, et al.
Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies[J].
Cell host & microbe, 2021.
[2] Dalamaga M , Karampela I, Mantzoros C S.
Commentary: Could iron chelators prove to be useful as an adjunct to COVID-19 Treatment Regimens?[J].
Metabolism, 2020, 108: 154260.
[3] Yuan M, Liu H, Wu NC , et al.
Structural basis of a shared antibody response to SARS-CoV-2[J].
Science, 2020, 369(6507): 1119-1123.
[4] Chan JFW, Zhang AJ, Yuan S, et al.
Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in a golden Syrian hamster model: implications for disease pathogenesis and transmissibility[J].
Clinical Infectious Diseases, 2020, 71(9): 2428-2446.
[5] https://hku.
hk/press/c_news_detail_22477.
html Author of this article | Ying Yuyan