New DCFHP alum COVID-19 vaccine candidate exhibits durable broad-spectrum protection in non-human primates

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed more than 6.89 million lives worldwide.

The rapid deployment of the COVID-19 vaccine has prevented an estimated 14 million deaths in the first year of administration. Following the emergence of new SARS-CoV-2 variants, efficacy of Existing COVID-19 vaccines are declining.

study: A ferritin-based COVID-19 nanoparticle vaccine that induces robust and durable broad-spectrum neutralizing antisera in non-human primates. Image credit: Marian Weyo / Shutterstock.com

Limitations of Current COVID-19 Vaccines

In May 2022, the World Health Organization (WHO) estimates that around 1 billion people worldwide are unvaccinated against COVID-19. The issue of affordability of the COVID-19 vaccine has severely limited mass vaccination. Most available vaccines require cold storage and transportation, which increases the cost of vaccine programs.

Lack of sustained immune protection following COVID-19 vaccination or natural infection has also hindered SARS-CoV-2 eradication. In addition, the emergence of SARS-CoV-2 variants of concern (VOCs) that can evade immune defenses induced either by vaccination or natural infection has led to a continual increase in infections worldwide.

S∆C-Fer COVID-19 vaccine

Previous studies have shown that nanotechnology-based protein vaccines are more readily available to antigen-presenting dendritic cells. Multivalent presentation of antigens facilitated by nanoparticles enhances receptor clustering and B cell activation.

Ferritin-based nanoparticle vaccines are associated with potent humoral immune responses against SARS-CoV-2 and significant efficacy and safety profiles. 1 protein nanoparticle-based vaccine, SΔC-Fer contains an inactivated polybasic cleavage site that has been shown to improve neutralization potency. Notably, SΔC-Fer also consists of a 2-proline (2P) prefusion stabilizing substitution that was present in the US Food and Drug Administration (FDA)-approved COVID-19 messenger ribonucleic acid (mRNA) vaccine.

The S∆C-Fer vaccine candidate also contains a deletion of 70 amino acid residues from the C-terminus of the spike ectodomain. This deletion allowed for highly flexible deletion of regions containing immunodominant linear epitopes.

Compared to other vaccines tested in mouse models, this modified spike protein on ferritin nanoparticles revealed a significantly superior neutralizing capacity of the induced antisera.

About research

Recent Nature Communications In this study, an updated version of SΔC-Fer called Delta-C70-Ferritin-HexaPro (DCFHP) was introduced. His previously present 2P-stabilizing substitutions were supplemented with 4 proline substitutions to develop the 6-proline substitution (HexaPro) form of the vaccine.

DCFHP can be produced in the Chinese Hamster Ovary (CHO) cell line. DCFHP was found to be more stable to heat denaturation than SΔC-Fer.

This nano-based COVID-19 vaccine contains DCFHP-alum, in which the DCFHP antigen was developed with aluminum hydroxide (alum). Aluminum salt adjuvants are commonly used adjuvants in human vaccines that have been approved by the FDA and other global regulatory bodies. Importantly, alum is also used in pediatric vaccines against diphtheria-tetanus-pertussis (DTaP), hepatitis B, and Haemophilus influenzae type b (Hib) and is associated with an exceptional safety profile.

Investigation result

DCFHP-alum was found to induce robust and sustained immune responses in mice against SARS-CoV-2 VOCs. Importantly, this vaccine candidate was stable over a wide range of temperatures from 4°C to 37°C for at least 14 days.

The low projected cost, large-scale production, and broad-spectrum antibody response make DCFHP-alum a desirable COVID-19 vaccine alternative. Thousands of DCFHP vaccine doses could be produced per liter of engineered CHO-K1 cell culture when vaccine doses of less than 100 micrograms and purification yields of 10% or more were obtained.

Rhesus monkeys that received two intramuscular doses of DCFHP alum were durable, robust and widely Neutralizing antibodyThese antibodies were highly effective against SARS-CoV-2 VOCs such as Omicron subspecies BA.4/5 and BQ, inducing balanced Th1 and Th2 immune responses. Importantly, these antibody responses persisted over 250 days.

Non-human primate (NHPs) antisera showed potent and sustained neutralizing activity against the SARS-CoV-1 pseudovirus. NHP one year later he also received a booster dose of DCFHP-alum. This generated robust, broad-spectrum and anamnestic neutralizing antibody responses.

Conclusion

A newly developed DCFHP-alum COVID-19 vaccine candidate was found to be affordable and effective for mass vaccination. Based on results, an infrequent annual booster vaccination schedule provides effective, robust and durable antibodies against the SARS-CoV-2 ancestral strain and its variants.

If the NHP results are replicated in clinical trials, DCFHP-alum could potentially be used as a booster vaccine for individuals receiving various SARS-CoV-2 vaccines. This vaccine candidate is also effective in people who have a history of COVID-19 and have not been vaccinated.