Phase I trial results from AdaptVac's COVID capsid virus-like particle vaccine

By Bhavana KunkalikarReviewed by Emily Henderson, B.Sc.Jan 22 2023

In a recent study published in The Lancet Microbe journal, researchers described the effectiveness of a modular capsid virus-like coronavirus disease 2019 (COVID-19) vaccination.

Study: First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2. Image Credit: NIAID

Background

Waning COVID-19 vaccination efficacy against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, continued transmission, and the lack of universal availability have necessitated the development of novel vaccines. Heterologous vaccination involving different COVID-19 vaccines is a method for extending the protection, yet, it has yielded no advantage over homologous boosters thus far.

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

About the study

In the present 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 sequential dose escalation trial with adjuvant selection. Participants aged 18 and 55 years who had no record of SARS-CoV-2 infection or COVID-19 vaccination were eligible. All participants were physically examined, hematologically and biochemically screened, and were assessed for current or prior infection with SARS-CoV-2, hepatitis B and C viruses, and human immunodeficiency virus (HIV).

The team administered two 0.5 mL intramuscular injections of ABNCoV2 delivered 28 days apart. The patients were followed-up on days 1, 4, 7, and 14 post-first vaccination and on days 42, 91, and 168 post-second immunization. Adverse events (AEs) were recorded using on-site visits, structured diaries, and daily reporting of body temperature for one week following each vaccination. Local and systemic adverse effects were reported for seven days following ABNCoV2 vaccination. Until the completion of the trial, adverse events, including severe adverse events (SAEs), were also reported.

The assignment to dosage and a combination of the vaccine with MF59- adjuvant was determined by the enrollment order. The predetermined escalation plan was initiated with 6 µg ABNCoV2 in groups 1A and 1B, which was 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 people, beginning with split cohorts for the initial three lowest doses. Each half of the cohort was treated with the non-adjuvanted vaccination, and the other half was administered the MF59-adjuvanted vaccine.

The major safety objective of the trial was the number of a minimum of probably related grade 3 AEs and SAEs from the initial ABNCoV2 vaccination to the conclusion of the follow-up period. Additionally, the secondary safety objective was the frequency and severity of AEs reported within one week of ABNCoV treatment.

Results

A total of 45 eligible SARS-CoV-2-naive participants were registered and assigned to one of the seven cohorts. Almost 44 individuals out of 45 completed all follow-ups. All the participants experienced a minimum of one AE. There were a total of 651 AEs occurrences, including 249 solicited AEs. Overall, the team noted that ABNCoV2 displayed considerable tolerance.

The level of RBD-specific antibodies declined progressively over the follow-up period and may be increased after vaccination with an approved SARS-CoV-2 vaccine among participants who were optimally dosed. After vaccination with two ABNCoV2 doses, RBD-specific CD4+ T cells were elicited. The team noted that the phenotype associated with the responding CD4+ T cells was primarily positive for interferon (IFN)-Ɣ, 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 lower CD4+ T-cell response than the 70 µg dose. Also, RBD-specific CD8+ T cells showed a marginal increase. Approximately 14 days following the second vaccination, significant in-vitro activity was shown by live virus neutralization tests. All ABNCoV2 dosages examined with and without adjuvant MF59 elicited 50% plaque reduction neutralization test (PRNT50) titers against FR-4286, a SARS-CoV-2 B.1 isolate that represented ancestral variants.

In a post-hoc examination, levels of in-vitro neutralizing activity were six times greater in adjuvanted vaccinees as compared to that in non-adjuvanted vaccinees. In addition, serum samples obtained from the 25 µg ABNCoV2 dosing groups that did and did not receive the MF59 adjuvant demonstrated robust cross-neutralization against the 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 (VOCs). Furthermore, the team found no decrease in the capacity to neutralize Alpha or Delta VOCs. However, a decrease of two-fold was noted against the Beta VOC. In an independent neutralization experiment, there was a 66-fold reduction in activity against the Omicron BA.1 sublineage when compared to the ancestral D614G strain.

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

Capsid virus-like particles (cVLP) r safe & immunogenic and versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2. Our paper in @LancetMicrobe @radboudumc_weet https://t.co/hjPf2ppjyD

— Heiman Wertheim (@HeimanW) January 19, 2023