Study: Humoral immunogenicity of a Coronavirus Disease 2019 (COVID-19) DNA Vaccine in Rhesus Macaques (Macaca mulatta) Delivered using Needle-free Jet Injection. Image Credit: ktsdesign / Shutterstock

Needle-free jet injection of new COVID-19 DNA vaccine shows promise in animal model

In a recent study published in bioRxiv*Server, researchers at the United States Army Medical Research Institute of Infectious Diseases evaluated the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) deoxyribonucleic acid (DNA) vaccine, nCOV-S (JET), in monkeys. Macaque rhesus. An earlier evaluation of a coronavirus disease 2019 (COVID-19) nucleic acid vaccine targeting the SARS-CoV-2 spike (S) protein elicited an appropriate humoral immune response in Syrian hamsters.

Stady: Humoral immunity to coronavirus disease 2019 (COVID-19) nucleic acid vaccine in Rhesus Macaques (Macaca mulatta) delivered using a needle-free jet syringe.. Image Credit: ktsdesign / Shutterstock

about studying

In the current study, the researchers hypothesised that nCOV-S (JET) would escalate a neutralizing antibody response when delivered by needle-free jet injection and traced evidence of its immunogenic capacity in rhesus macaques, a non-human (NHP) model.

They vaccinated test animals using two needle-free delivery methods. The first method used was a Stratis intramuscular (IM) device of 2 mg per vaccination dose. Second attempt intradermal delivery (ID) of 0.4 mg per vaccine using Tropis device. Stratis and Tropis devices delivered the vaccines as IM or ID puffs, respectively. The team measured inactivated antibodies obtained from the vaccine using two assays: 1) live viral plaque reduction neutralization tests (PRNT); b) Pseudomonas neutralization assays (PsVNA). In addition, they performed a multiplex immunoassay MAGPIX, which uses the SARS-CoV-2 S and S1 subunit, receptor-binding domain (RBD) and nucleocapsid proteins (NP).

The study used 12 Chinese-origin rhesus macaques aged between 8 and 15 years and weighing between five and 16 kilograms. Each vaccination group consisted of three males and three females randomly assigned. The team vaccinated all test animals on days 0, 21, and 42 and collected whole blood samples on days 0, 21, 35, 63 and 168. They monitored all test animals for clinical and behavioral aberrations daily.


Rhesus macaques need an additional (second) boost to reach a neutralizing antibody titer similar to that of the Syrian hamster. The mean geometric titer (GMT) or PsVNA50 in hamsters was around 640 after the two vaccinations, while it was 58 and 326 in rhesus macaques after two and three vaccinations, respectively. Similarly, the GMT PRNT50 in hamsters after the two vaccinations was approximately 640, while it was 24 and 71 in rhesus macaques after two and three vaccinations, respectively.

Neutralization and binding of antibody responses.  PRNT50, PsVNA50 and Magpix titers were collected from sera at different time points.  design.  (Blue arrows = vaccine doses, red drops = blood collection points).  b) Neutralization and binding of antibody values ​​at the indicated time points.  The lower scan boundaries are shown as a gray shaded area.

Neutralization and binding of antibody responses. PRNT50, PsVNA50 and Magpix titers were collected from sera at different time points. a) design. (Blue arrows = vaccine doses, red drops = blood collection points). B) Neutralization and binding of antibody values ​​at specified time points. The lower scan boundaries are shown as a gray shaded area.

It is noteworthy that DNA vaccines show higher immunity when administered intramuscularly than other methods. While hamsters received a total of 0.4 mg intramuscular nCOV-S (JET) over three vaccinations, NHPs received a six mg dose, implying that NHPs received an insufficient dose compared to hamsters on a weight basis.

However, this injectable DNA vaccine protects NHPs from disease. It neutralized antibody titers greater than 100, as measured by PsVNA. Another study tested a similar S-based DNA vaccine called ZyCoV-D in rabbits. Three doses of ID delivery using the Tropis device elicited a neutralizing antibody titer of 108, as assessed via the exact equilibrium test. Thus, neutralizing antibody titers obtained in NHPs appear to be comparable to titers that were protective in rabbits.

Furthermore, the nCOV-S (JET) vaccine delivered with an IM Stratis device showed cross-neutralizing activity against SARS-CoV-2 variants of concern (VOC), as assessed by PsVNA. All NHPs had a minimum PsVNA50 titer of 80 versus the SARS-CoV-2 strain WA-1, Beta and Delta VOCs. Notably, the titer of neutralizing antibodies against delta VOCs was the highest.

On the contrary, the DNA vaccine delivered by Tropis device had lower responses than the cross-linked VOCs. Only two animals (#7 and #9) showed cross-antibodies against all VOCs, as measured by PsVNA, and only #7 showed detectable antibodies against all VOCs tested by PRNT. Animals #7 and #9 also had the strongest antibody binding response, as measured by Magpix. Among its other benefits, the DNA nCOV-S (JET) vaccine was not formulated with lipid nanoparticles (LNPs) and did not require any adjuvants or electrical rationalization. I just used disposable non-needle syringes that are relatively inexpensive.


Future studies should explore ways to increase the potency of the DNA nCOV-S (JET) vaccine to enable its use as a stand-alone vaccine. However, for the doses used in the current study, it generated the desired neutralizing antibody responses after a two-dose regimen, making this vaccine more useful for heterogeneous boosting strategies. This vaccination strategy uses a booster vaccine from a different platform than that used to complete the primary vaccination series.

Several studies have demonstrated that heterogeneous enhancers induce similar reactions and more immunogenicity than homologous enhancers for all combinations. Therefore, on October 21, 2021, the US Food and Drug Administration (FDA) authorized the use of the mRNA-1273, Ad26.COV2.S, and BNT162b2 COVID-19 vaccines for use as heterogeneous vaccines. Similarly, a systematic review found that heterologous priming with BNT162b2 produced robust, reactive immunity that was tolerable. However, more research is warranted to establish optimal combinations, dosage regimens, and long-term safety profiles for heterogeneous vaccination strategies. To summarize, the current study confirmed the immunogenicity of the DNA nCOV-S (JET) vaccine and demonstrated its ability to elicit a rapid humoral immune response in NHPs.

*Important note

bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behaviour, or be treated as established information.

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