Results of Phase 3 Nanocovax SARS-CoV-2 vaccine trial suggest robust effectiveness

A recent study posted to the medRxiv* preprint server presented the findings of the Phase 3 trial of the Nanocovax coronavirus disease 2019 (COVID-19) vaccine.

Study: The efficacy, safety and immunogenicity Nanocovax: results of a randomized, double-blind, placebo-controlled Phase 3 trial. Image Credit: Prostock-studio/Shutterstock
Study: The efficacy, safety and immunogenicity Nanocovax: results of a randomized, double-blind, placebo-controlled Phase 3 trial. Image Credit: Prostock-studio/Shutterstock

Background

Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine. It consists of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) with aluminum hydroxide adjuvant. It has generated substantial levels of anti-S antibodies (Abs) in prior monkey and rodent models.

Micro-neutralization assays were used to assess neutralizing Ab titers of Nanocovax against both the SARS-CoV-2 original strain and the Delta variant. The vaccine was proven to generate a significant immunological response and be safe in healthy adult volunteers in Phase 1 and 2 trials.

About the study

In the present study, the researchers reported the results of a randomized, multicenter, placebo-controlled, and double-blind Phase 3 investigation of the Nanocovax vaccine initiated in June 2021. The trial assessed the immunogenicity, safety, and prophylactic effectiveness of the 25mcg of Nanocovax vaccine against SARS-CoV-2 in nearly 13,007 subjects.

The Phase 3 investigation was executed by the Pasteur Institute in Ho Chi Minh City and Military Medical University in Ha Noi at four research sites in Vietnam, consisting of Ha Noi and Long An, Tien Giang, and Hung Yen provinces.

Non-pregnant women and men who were at least 18 years old and had a body mass index (BMI) of 16-41 kg/m2 were eligible for the study. The participants were divided into three age groups: 18 to 45 years, 46 to 60 years, and above 60 years.

Nanocovax's immunogenicity was evaluated based on surrogate virus neutralization, anti-S immunoglobulin G (IgG) Ab response, kinds of helper T cell response, and wild-type SARS-CoV-2 neutralization from intracellular staining (ICS) for interleukin-4 (IL-4) and interferon γ (IFN-γ). The vaccine effectiveness (VE) was computed based on serologically verified COVID-19 cases.

Results and discussions

The results showed that until day 180, the placebo and vaccine groups had equal rates of unsolicited and solicited adverse events (AE). Among the 13,007 volunteers distributed in placebo and vaccine cohorts, 100 serious adverse events (SAE) were detected. While the experimental products were unrelated to 96 of these 100 SAEs, the investigators and the Data and Safety Monitoring Board (DSMB) members established that four SAEs were probably vaccine-related. 

Most of the documented AEs were Grade 1 and vanished within two days following vaccination. In the majority of subjects, reactogenicity of systemic and local AEs was nonexistent or low and had a short duration. These data illustrate Nanocovax's exceptional safety profile.

Nanocovax elicited strong neutralizing Ab and IgG responses in terms of immunogenicity. On day 42, neutralizing Ab and anti-S-IgG levels titers were much greater than the naturally infected COVID-19 subjects. On day 42, the geometric mean fold rise (GMFR) of anti-S IgG was above 218, relative to the initial level on day 0.

In line with prior research, a decrease in the neutralizing Ab levels against the SARS-CoV-2 Delta and Alpha variants was observed in this trial. This decline correlated with lower VE in this investigation, where the dominant SARS-CoV-2 variant was Delta. 

Nanocovax induced both the T-helper-2 and -1 (Th2 and Th1) responses. Nevertheless, Nanocovax was observed to trigger Th2 polarization rather than Th1 polarization. Ab-dependent enhancement was an issue with Th2 polarization (ADE). This risk has been addressed partially by prior vaccine research in hamster models infected with SARS-CoV-2 and the licensure of therapeutic Abs for SARS-CoV-2 treatment. Notably, in this Nanocovax experiment, ADE was not detected across patients in the vaccine cohort.

According to the post-hoc evaluation, the VE against symptomatic illness was 51.5%. The VE in preventing critical disease and mortality was 93.3%. Although the lower limit of the VE confidence interval was less than 50%, it fulfilled the Food and Drug Administration (FDA) requirements for the SARS-CoV-2 vaccine development, stating the lower bound of the VE confidence interval to be more than 30%.

Limitations

This Phase 3 trial of Nanocovx had several drawbacks. The factors that posed hurdles in Nanocovax's VE evaluation include 1) emergence of the SARS-CoV-2 Delta variant, 2) government regulations, such as vaccine mandates irrespective of the vaccine trial participation, and strict quarantine, and 3) differences in SARS-CoV-2 surveillance at various research locations. 

Other limitations include a lack of ethnic variety (all volunteers were Vietnamese), a small sample size, and a short follow-up period. In actuality, the sponsor, the Ethics Committee, and the lead investigators opted to halt the trial in December 2022, one year ahead of schedule. This was due to ethical concerns, particularly the safety of subjects. After this date, the subjects were given authorized emergency use COVID-19 vaccinations.

Overall, the study findings demonstrated that the Nanocovax 25mcg COVID-19 vaccine had robust effectiveness, safety, and immunogenicity against COVID-19 with 51.5% efficacy against Delta infections.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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