Needle‐free injection system delivery of ZyCoV‐D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS‐CoV‐2

Abstract

The apprehension of needles related to injection site pain, risk of transmitting bloodborne pathogens, and effective mass immunization have led to the development of a needle‐free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCoV‐D in rhesus macaques against SARS‐CoV‐2 infection. Briefly, 20 rhesus macaques were divided into 5 groups (4 animals each), that is, I (1 mg dose by NIS), II (2 mg dose by NIS), III (1 mg dose by NFIS), IV (2 mg dose by NFIS) and V (phosphate‐buffer saline [PBS]). The macaques were immunized with the vaccine candidates/PBS intradermally on Days 0, 28, and 56. Subsequently, the animals were challenged with live SARS‐CoV‐2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5, and 7 days post infection from each animal to determine immune response and viral clearance. Among all the five groups, 2 mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers postvirus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post‐SARS‐CoV‐2 challenge and significant immune response in the immunized animals demonstrated the efficiency of NFIS in delivering 2 mg ZyCoV‐D vaccine candidate.

High-Pressure Delivery of Oncolytic Viruses via Needle-Free Injection Preserves Therapeutic Activity

“…Furthermore, several lines of evidence indicate that this injection method can elicit robust immune responses upon vaccine administration. For example, when a needle-free injection system was used to administer the ZyCoV-D DNA or mRNA-based vaccine against SARS-CoV-2, significant antibody titers and immune responses were observed [19,29]. These responses included elevated levels of IgG and neutralizing antibodies, enhanced lymphocyte proliferation, and cytokine responses [19,29].…”

To be remembered: B cell memory response against SARS‐CoV‐2 and its variants in vaccinated and unvaccinated individuals

“…87,94 Notably, a dose-dependent increase in IgG and T cell response has been observed in Rhesus macaques by this vaccine. 95 87 These VLPs offer a distinct presentation of functional antigens, resembling natural infections and possibly stimulating highly effective B cell immune reactions. A study about the immunogenicity of AS03-adjuvanted VLP-based vaccine suggests that the Th2-type response triggered by VLPs could contribute to high levels of neutralizing antibodies and enduring memory B cell responses.…”

“…Currently, only one DNA vaccine for COVID‐19, ZyCoV‐D is approved by WHO which was developed by Zydus Cadila in India 87,94 . Notably, a dose‐dependent increase in IgG and T cell response has been observed in Rhesus macaques by this vaccine 95 . Studies on B cell memory response after immunization with DNA vaccines are not in the literature as yet.…”

An Overview of SARS-CoV-2 Etiopathogenesis and Recent Developments in COVID-19 Vaccines

“…The vaccine was reported to be efficient against several variants of SARS-CoV-2, up to the delta variant [41,59,60]. The DNA vaccines were delivered intradermally; currently, the administration of these vaccines is moved from a needle injection system to a needlefree injection system with improved immunogenicity and protective efficacy mediated by both the humoral and cell-mediated immunity [61,62].…”

“…The logic behind the mRNA vaccines is to deliver specific SARS-CoV-2 mRNA, such as the one that codes for S protein, to be translated in the host cell. The viral protein thus formed will be further processed by the host proteosome mechinery for presentation to the immune system to elicit humoral and cellular-immunity against subsequent infection [61,62]. Current mRNA vaccines for COVID-19 can be classified into three types namely non-replicating mRNA, self-amplifying mRNA (saRNA), and circular RNA (cir-cRNA).…”