Results from Phase I Trial of AdaptVac’s COVID Capsid Virus-Like Particle Vaccine

In a recent study published in lancet microbe Journal, researchers described the efficacy of modular capsid virus-like coronavirus disease 2019 (COVID-19) vaccination.

study: First Human Use of a Modular Capsidvirus-Like Vaccine Platform: An Open-Label, Non-Randomized, Phase 1 Clinical Trial of the SARS-CoV-2 Vaccine ABNCoV2Image Credit: NIAID

Background

Decline in COVID-19 vaccination Effectiveness The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutation, continued transmission, and lack of universal availability necessitate the development of new vaccines. Heterologous vaccination containing different COVID-19 vaccines is a method for extending protection, but so far has no advantage over allogeneic boosters.

The team developed a proprietary modular vaccination platform that utilizes capsid virus-like particles (cVLPs) as antigen-presenting scaffolds. By adding his SARS-CoV-2 spike receptor binding domain (RBD) to this cVLP platform, his COVID-19 vaccine, called ABNCoV2, was developed. ABNCoV2 was immunogenic and showed high productivity. Neutralizing antibody Potency in preclinical studies with mice.

About research

In this study, researchers evaluated the safety, immunogenicity, and tolerability of ABNCoV2 in SARS-CoV-2-naive participants.

The team described COUGH-1, a Phase 1 and escalating dose trial with adjuvant selection. Participants aged 18 and 55 with no record of SARS-CoV-2 infection or COVID-19 vaccination were eligible. All participants will undergo physical examination, hematological and biochemical screening, and be evaluated for current or previous infection with SARS-CoV-2, hepatitis B and C virus, and human immunodeficiency virus (HIV) it was done.

The team administered two 0.5 mL intramuscular injections of ABNCoV2 28 days apart. Patients were followed on days 1, 4, 7, and 14 after the first vaccination and on days 42, 91, and 168 after the second vaccination. Adverse events (AEs) were recorded using site visits, structured diaries, and daily reporting of her temperature for 1 week after each vaccination. Local and systemic adverse effects were reported 7 days after ABNCoV2 vaccination. Adverse events, including serious adverse events (SAEs), were also reported until study completion.

Allocation of vaccine and MF59 adjuvant to doses and combinations was determined by order of enrollment. The prescribed escalation schedule started with 6 μg ABNCoV2 in groups 1A and 1B, followed by 12 μg in groups 2A and 2B. 25 μg in groups 3A, 3B, and 6; 50 μg in groups 4 and 7; 70 µg in group 5; Dose escalation was performed in groups of 6 starting with the first 3 lowest dose split cohorts. Each half of the cohort was treated with non-adjuvanted vaccination and the other half received the MF59 adjuvanted vaccine.

The primary safety goal of this trial was the minimum number of possibly related grade 3 AEs and SAEs from the first ABNCoV2 vaccination to the end of the follow-up period. In addition, a secondary safety goal was the frequency and severity of AEs reported within his week of ABNCoV treatment.

result

A total of 45 eligible SARS-CoV-2-naive participants were enrolled and assigned to one of seven cohorts. Nearly 44 of 45 completed all follow-ups. All participants experienced at least one of her AEs. A total of 651 AEs were raised, including 249 claimed AEs. Overall, the team noted that ABNCoV2 showed considerable resistance.

Levels of RBD-specific antibodies may decline gradually over the follow-up period and increase after vaccination with the approved SARS-CoV-2 vaccine among optimally dosed participants. After her two doses of ABNCoV2, RBD-specific CD4+ T cells pulled out. The team noted that the phenotype associated with responding CD4+ T cells was predominantly interferon (IFN)-Ɣ positive, with the majority of cells co-expressing CD137 and tumor necrosis factor (TNF) .

The 50 μg dose of vaccine produced a significant more CD4+ T cell response than the 25 μg dose and a lower CD4+ T cell response than the 70 μg dose. Also, RBD-specific CD8+ T cells showed a slight increase. Approximately 14 days after the second vaccination, a live virus neutralization test showed significant in vitro activity. All ABNCoV2 doses tested with or without the adjuvant MF59 induced plaque reduction neutralization test (PRNT50) titers of 50% against FR-4286.

In a post hoc study, the level of in vitro neutralizing activity was 6-fold greater in adjuvanted vaccinees compared to non-adjuvanted vaccinees. In addition, serum samples obtained from the MF59 adjuvant-treated group and his ABNCoV2-treated group at 25 μg without the adjuvant were positive for the B.1 isolate and SARS-CoV-2 alpha (B.1.1.7). showed strong cross-neutralization. Variant (VOC) of Beta (B.1.351), and Delta (B.1.617.2). Additionally, the team found no reduction in its ability to neutralize alpha or delta VOCs. However, he had a 2-fold reduction in beta VOCs. An independent neutralization experiment showed a 66-fold reduction in activity against the Omicron BA.1 subline compared to his ancestral D614G strain.

Overall, the study results showed that ABNCoV2 exhibited considerable resistance and induced substantial virus-neutralizing antibody responses after a second vaccination in healthy SARS-CoV-2-naive individuals. believe that these results will facilitate the further development of ABNCoV2 as an effective second-generation vaccine and demonstrate the efficiency of the modular cVLP platform.

Capsid virus-like particles (cVLPs) r Safe, immunogenic, and versatile platforms to combat pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in SARS-CoV-2-naive individuals.our paper @LancetMicrobe @radboudumc_weet https://t.co/hjPf2ppjyD

— Heiman Wertheim (@HeimanW) January 19, 2023