Spike DNA co-immunization in rhesus macaques for control of Covid-19

Debarati Basu, Makaut WB

Vaccines derived from mRNA have greater versatility and efficacy for preventing Covid-19 infections. An effective alternative is DNA vaccines. It is used as it can induce humoral and cellular immune responses in animal models. They can also be utilized in human trials. The efficacy and immunogenicity of DNA-based vaccines were tested. The development of pike antigens occurs when the intramuscular injection is applied followed by the process of electroporation in rhesus macaques.

Various spike DNA vaccines procedure functions by antibody production that strongly neutralizes SARS-CoV-2 in vitro. It further induces vigorous T-cell responses. The antibodies then recognize and neutralize a group of various Spike variants. The spike variants mainly include Alpha, Delta, Epsilon, Eta, and A.23.1. It contains a small extent of Beta and Gamma spike variants also. A comparison was done between the regimen of DNA-based vaccines and co-immunization of Spike DNA regimen and protein located in the same anatomical site. Greater antibody responses were recorded for the latter one.

Control of SARS-CoV-2 in the intranasal channel is carried by all of the vaccine regimens. It also prevents the presence of viruses in the lower respiratory tract. Transient virus levels present in the nasal mucosa are inversely correlated with the vaccine-induced binding and neutralizing antibodies and also antibodies that induce cellular phagocytosis. One of the important properties of the Spike DNA+Protein co-immunization regimen is that it induces the greatest binding of antibodies. It also neutralizes antibodies. It is highly effective and can control Covid-19 in rhesus macaques.

Significance of the study:

Antibodies that are neutralized by anti-spike prove protection against Covid-19 infections in animal models as well as humans. It also provides high humoral immunity which acts as an important factor for protection. The study shows there are strong antibody and T cell responses by various Spike DNA-based vaccine procedures. It gives strong protection and control against Covid-19 infection. This is usually present in the rhesus macaque model. The study further provides information to compare vaccines that induce different humoral and cellular immune responses. It also helps in the development of long-lasting immunity against Covid-19 infections.

An alternative vaccine is obtained from alphavirus which is obtained from replicon RNA (repRNA). This vaccine provides robust anti-Spike humoral immune responses. This model is also being utilized clinically. One advantage of the DNA+Protein co-immunization procedure is that it provides maximum humoral and cellular immune responses. The vaccine is effective against Simian Immunodeficiency Virus (SIV) infections. It is also effective against the hybrid Simian Immunodeficiency Virus (SIV) model. This model is applied in rhesus macaques. The rhesus model used is of Indian origin.

Findings of the study:

Spike DNA and Spike DNA+Protein vaccination of rhesus macaques

The DNA-based vaccines induce strong Spike proteins that generate humoral and cellular responses. These responses also include cytotoxic T cell responses. It was also shown that the DNA+Protein co-immunization regimen induces the highest antibody levels in animals that were injected with them.

Effector function of Spike DNA vaccine-induced antibodies

It is shown the in vitro assays have DNA vaccines encoded by spike proteins. It induces Nab which controls Covid-19 infections. It is further shown that DNA+Protein immunization showed the highest antibody responses.

Conclusion:

The study showed two types of Covid-19 vaccines one was DNA-based only and the other was co-immunization of DNA and protein. The immunogenicity of DNA vaccines was measured by stabilized Spike proteins. The spike proteins differ by their presence or absence in the cleaving site and C-terminal of mice or rhesus model. One important factor of DNA+Proteins co-immunization procedures is that they provide effective virological control of the respiratory tract specifically of the upper regions.

DNA+Protein immunization showed the highest antibody responses when induced on the same site as obtained from studies on HIV/SIV DNA+Protein co-immunization. They also induce T cell responses and also generate strong anti-Spike antibody responses after a single vaccination. Protection from Covid-19 infections highly depends on the vaccine-generated immune responses in mucosal tissues. 

The study showed the difference in efficacy levels between 2or 3 Spike DNA vaccines. The data also showed after 2 immunizations there is a diminished efficacy during the initial control. It is due to the difference in the mucosal immune responses of the two regimens. The best protective response occurs after three-dose DNA+Protein co-immunization, it also provides rapid control of Covid-19 infections.

One of the disadvantages of this study is that there is a difference between vaccine procedures, animal facilities, and procedures to monitor immune responses, virus stocks, and so on. Challenges are faced while virus load measuring and so it is difficult to make a comparative report on NHP studies. Protective immunity is induced by SARS-CoV-2 Spike protein is also an immunogen. The study does not provide the data on the duration of the protective immunity which includes balance immune responses as well as cellular immune responses. But it is said that DNA vaccination may extend protective immunity.

Also read: Natural infection of Influenza produces effective antibodies against multiple strains

Reference:

1. Rosati, M., Agarwal, M., Hu, X., Devasundaram, S., Stellas, D., Chowdhury, B., Bear, J., Burns, R., Donohue, D., Pessaint, L., Andersen, H., Lewis, M. G., Terpos, E., Dimopoulos, M. A., Wlodawer, A., Mullins, J. I., Venzon, D. J., Pavlakis, G. N., & Felber, B. K. (2021). Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques. PLOS Pathogens, 17(9), e1009701. https://doi.org/10.1371/journal.ppat.1009701

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