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

In a recently published study bioRxiv* Server, researchers from the United States Army Medical Research Institute of Infectious Diseases evaluated the immunogenicity of a deoxyribonucleic acid (DNA), nCOV-S(JET) coronavirus 2 (SARS-CoV-2) vaccine in rhesus monkeys. A previous evaluation of this coronavirus disease 2019 (COVID-19) DNA vaccine, targeting the SARS-CoV-2 spike (S) protein, elicited an adequate humoral immune response in Syrian hamsters.

Study: Humoral immunogenicity of a DNA vaccine against coronavirus disease 2019 (COVID-19) in rhesus monkeys (Macaca mulatta) administered by needle-free jet injection. Photo Credit: ktsdesign/Shutterstock

About the study

In the current study, researchers hypothesized that nCOV-S(JET) would elicit a detectable neutralizing antibody response when administered via needle-free jet injection and pursued evidence of its immunogenicity in rhesus monkeys, a non-human primate model (NHP ).

They vaccinated the test animals using two needle-free delivery methods. The first method used was the Stratis device for intramuscular (IM) administration of 2 mg per vaccine dose. The second attempt at intradermal (ID) administration of 0.4 mg per inoculation using the Tropis device. The Stratis and Tropis devices delivered liquid jet vaccines IM and ID, respectively. The team measured vaccine-elicited neutralizing antibodies using two assays: i) live virus plaque reduction neutralization (PRNT) assays; ii) Pseudovirion neutralization assays (PsVNA). In addition, they performed a MAGPIX multiplex immunoassay using the SARS-CoV-2 proteins S, S1 subunit, receptor binding domain (RBD) and nucleocapsid (NP).

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

study results

Rhesus monkeys required an additional (second) boost to reach similar neutralizing antibody titers as Syrian hamsters. The geometric mean titre (GMT) or PsVNA50 in hamsters was about 640 after two vaccinations, while in rhesus monkeys it was 58 and 326 after two and three vaccinations, respectively. Likewise, the GMT PRNT50 in hamsters was about 640 after two vaccinations, while in rhesus monkeys it was 24 and 71 after two and three vaccinations, respectively.

Neutralizing and binding antibody responses. PRNT50, PsVNA50 and Magpix titers from sera collected at different time points. A) Draft. (blue arrows = vaccine dosage; red drops = blood sampling times). b) Neutralizing and binding antibody values ​​at the times indicated. Lower sample limits are shown as a gray shaded area.

It is noteworthy that DNA vaccines show the highest immunogenicity when administered IM compared to other routes. While hamsters received a total of 0.4 mg nCOV-S(JET) intramuscularly over three vaccinations, NHPs received a dose of six mg, meaning that the NHPs received an insufficient dose per weight compared to the hamsters.

Nonetheless, this needle-injected DNA vaccine protected NHPs from disease. It elicited neutralizing antibody titers in excess of 100 as measured by a PsVNA. Another study tested a similar S-based DNA vaccine called ZyCoV-D in rabbits. Three doses of its ID administration using the Tropis device elicited a neutralizing antibody titer of 108 as determined by a microneutralization assay. Thus, the neutralizing antibody titers elicited in NHPs appear to be comparable to titers that were protective in rabbits.

In addition, the nCOV-S(JET) vaccine administered with the IM Stratis device showed cross-neutralizing activity against SARS-CoV-2 variants of concern (VOC) according to the PsVNA assessment. All NHPs had a PsVNA50 titer of at least 80 against SARS-CoV-2 WA-1 strain, beta and delta VOCs. Notably, neutralizing antibody titers were highest to Delta VOC.

In contrast, the DNA vaccine delivered by a Tropis device ID had lower cross-neutralizing VOC responses. Only two animals (#7 and #9) showed cross-neutralizing antibodies to all VOCs as measured by PsVNA and only #7 showed detectable cross-neutralizing antibodies to all VOCs tested by PRNT. Animals #7 and #9 also showed the most robust antibody binding response as measured by the Magpix. Among other advantages, the nCOV-S(JET) DNA vaccine was not formulated with lipid nanoparticles (LNPs) and required neither adjuvant nor electroporation. Only relatively inexpensive disposable needleless syringes have been used.

Conclusions

Future studies should investigate ways to increase the effectiveness of the nCOV-S(JET) DNA vaccine to allow its use as a standalone vaccine. However, for the doses used in the current study, it produced the desired neutralizing antibody responses following a two-dose regimen, making this vaccine the most beneficial for heterologous booster strategies. This vaccination strategy uses a booster vaccine from a different platform than that used to complete the primary series.

Several studies have shown that heterologous boosters elicit similar reactogenicity and more immunogenicity than homologous boosters for all combinations. Therefore, as early as October 21, 2021, the US Food and Drug Administration (FDA) approved the use of mRNA-1273, Ad26.COV2.S and BNT162b2 COVID-19 vaccines for use as heterologous boosters. Likewise, a systemic review revealed that heterologous priming with BNT162b2 produced robust immunogenicity and tolerable reactogenicity. However, more research is needed to determine optimal combinations, dosing regimens, and long-term safety profiles of heterologous vaccination strategies. In conclusion, the current study confirmed the immunogenicity of the nCOV-S(JET)-DNA vaccine and demonstrated its potential to elicit a rapid humoral immune response in NHPs.

*Important NOTE

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