AdaptVac COVID Capsid Virus-Like Particle Vaccine Phase I Trial Results

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

To study: First-in-human use of a modular capsid virus vaccine platform: an open-label, non-randomized phase 1 clinical trial of the SARS-CoV-2 ABNCoV2 vaccine. Image credit: NIAID

Background

COVID-19 vaccination down efficiency against emerging mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continued transmission and lack of universal availability have necessitated the development of new vaccines. Heterologous vaccination involving different COVID-19 vaccines is one method to extend protection, but has so far yielded no advantage over homologous boosters.

The team developed a unique modular vaccination platform using capsid virus-like particles (cVLPs) as antigen-presenting scaffolds. By attaching the spike receptor binding domain of SARS-CoV-2 (RBD) to this cVLP platform, a COVID-19 vaccine called ABNCoV2 was developed. ABNCoV2 showed immunogenicity and produced a strong neutralizing antibody titers in preclinical tests with mice.

About the study

In the present study, researchers assessed the safety, immunogenicity, and tolerability of ABNCoV2 in SARS-CoV-2 naïve participants.

The team described COUGH-1, a Phase 1, sequential dose-escalation trial with adjuvant selection. Participants aged 18 and 55 who had no record of SARS-CoV-2 infection or COVID-19 vaccination were eligible. All participants underwent a physical examination, blood and biochemical screening, and were evaluated for current or previous infection with SARS-CoV-2, hepatitis B and C viruses, and human immunodeficiency virus ( HIV).

The team administered two 0.5ml intramuscular injections of ABNCoV2 given 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 body temperature reports for one week after each vaccination. Local and systemic adverse reactions were reported for seven days after ABNCoV2 vaccination. Until the end of the trial, adverse events, including serious adverse events (SAEs), were also reported.

Assignment to dosage and to a combination of vaccine with MF59 adjuvant was determined by order of listing. The pre-determined escalation plan was initiated with 6 µg of 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; and 70 µg in Group 5. Dose escalation was conducted in groups of six, starting with split cohorts for the first three lowest doses. Each half of the cohort was treated with the unadjuvanted vaccine and the other half received the MF59-adjuvanted vaccine.

The primary safety objective of the trial was the minimum number of likely related AEs and Grade 3 SAEs between the initial ABNCoV2 vaccination and the end of the follow-up period. Additionally, the secondary safety endpoint was the frequency and severity of AEs reported within one week of ABNCoV treatment.

Results

A total of 45 eligible SARS-CoV-2 naïve participants were registered and assigned to one of seven cohorts. Nearly 44 out of 45 people completed all the follow-ups. All participants experienced at least one AE. There were a total of 651 AR occurrences, including 249 solicited ARs. Overall, the team noted that ABNCoV2 displayed considerable tolerance.

The level of RBD-specific antibodies decreased gradually during the follow-up period and may be increased after vaccination with an approved SARS-CoV-2 vaccine in participants who received an optimal dose. After vaccination with two doses of ABNCoV2, RBD-specific CD4+ cells T cells were aroused. 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 the vaccination generated a more significant CD4+ T cell response than the 25 µg dose and a weaker CD4+ T cell response than the 70 µg dose. Also, RBD-specific CD8+ T cells showed a marginal increase. Approximately 14 days after the second vaccination, significant in vitro activity was demonstrated by live virus neutralization assays. All doses of ABNCoV2 examined with and without MF59 adjuvant elicited plaque reduction neutralization test titers of 50% (PRNT50) against FR-4286, a SARS-CoV-2 B.1 isolate that represented ancestral variants .

In post-hoc examination, levels of in vitro neutralizing activity were six times higher in vaccinees with adjuvant than in vaccinees without adjuvant. Additionally, serum samples obtained from the 25 μg ABNCoV2 assay groups that received and did not receive MF59 adjuvant demonstrated robust cross-neutralization against B.1 isolates as well as SARS-CoV- 2 Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants of concern (COV). Additionally, the team found no decrease in the ability to neutralize Alpha or Delta VOCs. However, a double decrease was noted compared to the Beta VOC. In an independent neutralization experiment, there was a 66-fold reduction in activity against the Omicron BA.1 subline compared to the ancestral D614G strain.

Overall, the study results indicated that ABNCoV2 displayed considerable tolerance and elicited significant virus-neutralizing antibody responses after the second vaccination in SARS-CoV-2 naïve healthy individuals. The researchers believe that these results encourage the further development of ABNCoV2 as an effective second-generation vaccine and demonstrate the efficacy of the modular cVLP platform.

Capsid virus-like particles (cVLPs) are a safe, immunogenic, and versatile platform for fighting pandemics. Our goal was to clinically test a modular cVLP COVID-19 vaccine in SARS-CoV-2 naïve individuals. Our paper in @LancetMicrobe @radboudumc_weet https://t.co/hjPf2ppjyD

— Heiman Wertheim (@HeimanW) January 19, 2023