In a recent study published on bioRxiv*server, researchers at the United States Army Medical Research Institute of Infectious Diseases evaluated the immunogenicity of a deoxyribonucleic acid (DNA) vaccine against coronavirus 2 (SARS-CoV-2) severe acute respiratory syndrome, nCOV-S(JET), in rhesus macaques. A previous evaluation of this DNA vaccine against coronavirus disease 2019 (COVID-19) targeting the spike (S) protein of SARS-CoV-2 elicited an adequate humoral immune response in Syrian hamsters.
Study: Humoral immunogenicity of a DNA vaccine against coronavirus disease 2019 (COVID-19) in rhesus macaques (Macaca mulatta) administered by needleless injection. Image Credit: ktsdesign/Shutterstock
About the study
In the current study, researchers hypothesized that nCOV-S(JET) would mount a detectable neutralizing antibody response when administered by needleless jet injection and searched for evidence of its immunogenicity in rhesus macaques, a non-human primate (NHP) model.
They vaccinated test animals using two needleless delivery methods. The first method used was the Stratis device to administer intramuscularly (IM) 2 mg per vaccination dose. The second attempt at intradermal (ID) administration of 0.4 mg by vaccination with the Tropis device. The Stratis and Tropis devices delivered vaccines as an IM or ID liquid jet, respectively. The team measured vaccine-induced neutralizing antibodies using two tests – i) live viral plaque reduction neutralization (PRNT) assays; ii) pseudovirion neutralization assays (PsVNA). Additionally, they performed a MAGPIX multiplex immunoassay, which uses SARS-CoV-2 S, S1 subunit, receptor binding domain (RBD), and nucleocapsid (NP) proteins.
The study used 12 rhesus macaques of Chinese descent aged 8 to 15 years and weighing between 5 and 16 kilograms. Each vaccination group included three randomly assigned male and three female animals. 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 abnormalities clinical and behavioral.
The rhesus macaques needed an extra (second) boost to achieve similar neutralizing antibody titers as the Syrian hamsters. The geometric mean titer (GMT) or PsVNA50 in hamsters was approximately 640 after two vaccinations, while it was 58 and 326 in rhesus macaques after two and three vaccinations, respectively. Similarly, the GMT PRNT50 in hamsters after two vaccinations was around 640, while it was 24 and 71 in rhesus macaques after two and three vaccinations, respectively.
Neutralizing and binding antibody responses. PRNT50, PsVNA50 and Magpix titers of sera collected at different times. A) Design. (blue arrows = vaccine dosage; red drops = blood collection points). B) Neutralizing and binding antibody values at time points indicated. The lower assay limits are represented by a shaded area.
It should be noted that DNA vaccines show the highest immunogenicity when administered IM compared to other routes. While hamsters received a total of 0.4 mg of nCOV-S(JET) intramuscularly over three vaccinations, NHPs received a 6mg dose, implying that NHPs received an inadequate dose compared to to hamsters on a per weight basis.
Nevertheless, this DNA vaccine administered by needle injection protected NHPs from the disease. It elicited neutralizing 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 his ID administration using the Tropis device elicited a neutralizing antibody titer of 108, as assessed via a microneutralization assay. Thus, the neutralizing antibody titers induced in NHPs appear comparable to the protective titers in rabbits.
Additionally, the nCOV-S(JET) vaccine administered using the IM Stratis device exhibited cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs), as assessed by PsVNA. All NHPs had a minimum PsVNA50 titer of 80 against SARS-CoV-2 strain WA-1, beta and delta COVs. Notably, neutralizing antibody titers against Delta VOC were the highest.
In contrast, the DNA vaccine delivered ID by the Tropis device had weaker cross-neutralizing COV responses. Only two animals (#7 and #9) showed cross-neutralizing antibodies against all VOCs as measured by PsVNA, and only #7 showed detectable cross-neutralizing antibodies against all VOCs tested by PRNT. Animals #7 and #9 also had the most robust antibody binding response as measured by the Magpix. Among its other advantages, the nCOV-S(JET) DNA vaccine was not formulated with lipid nanoparticles (LNPs) and required no adjuvant or electroporation. He simply used relatively inexpensive needleless disposable syringes.
Future studies should explore ways to increase the potency of the nCOV-S DNA vaccine (JET) to enable its use as a stand-alone vaccine. However, for the assays used in the present study, it generated the desired neutralizing antibody responses after a two-dose regimen, making this vaccine the most beneficial for heterologous boosting strategies. This vaccination strategy uses a booster vaccine from a different platform than that used to complete the primary vaccination.
Several studies have shown that heterologous boosters induce similar reactogenicity and more immunogenicity than homologous boosters for all combinations. Therefore, on October 21, 2021, the United States Food and Drug Administration (FDA) cleared mRNA-1273, Ad26.COV2.S, and BNT162b2 COVID-19 vaccines for use as heterologous boosters. Similarly, a systemic review found that heterologous priming with BNT162b2 produced robust immunogenicity and tolerable reactogenicity. Still, more research is needed to establish optimal combinations, dosing regimens, and long-term safety profiles of heterologous vaccination strategies. In summary, the present study confirmed the immunogenicity of the nCOV-S(JET) DNA vaccine and showed its potential to elicit a rapid humoral immune response in NHPs.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.
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