Hope for the future? Ferritin nanoparticle vaccines protect against all SARS-CoV-2 variants

While the rapid development of COVID vaccines is a scientific victory, there is still a need for a globally available vaccine that can provide lasting immunity
against current and future SARS-CoV-2 variants (VOCs).
。 Here, in a paper in bioRxiv, researchers at Stanford University describe DCFHP, a ferritin-based protein nanoparticle vaccine candidate, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP alum), to trigger potent and durable neutralizing antiserum
against known VOCs (including Omicron BQ.
1) as well as SARS-CoV-1 in non-human primates.
After receiving a booster dose within one year of primary immunization, DCFHP alum causes a strong memory response
.

An updated version of SΔC-Fer, called Delta-C70-Ferritin-HexaPro or DCFHP
.
The new vaccine is supplemented with four previously described 26 proline substitutions to create six proline-substituted (HexaPro) versions of the vaccine
.
Previous studies have shown that the HexaPro SARS-CoV-2 spike protein has increased stability and expression
relative to the 2P version.
DCFHP is more stable
to thermal denaturation than SΔC-Fer.
DCFHP can be produced
in Chinese hamster ovary (CHO) cell lines at levels in excess of 2 g/L.
DCFHP alum has the potential to serve as an annual booster vaccine and as a primary vaccine
for children, including infants.

The new vaccine formulation, DCFHP alum, consists of DCFHP antigens formulated with aluminum hydroxide (Alhydrogel™), the most commonly used adjuvant in human vaccines licensed by the FDA and regulatory agencies around the world and administered to billions of people over the past 90 years
.
In addition, aluminum salt adjuvants are currently used as infant vaccines for the prevention of hepatitis B, diphtheria-tetanus-pertussis (DTaP), Haemophilus influenzae type b (Hib), and pneumococcal infectious agent 34 with a favorable safety profile
.

DCFHP alum elicited a robust and durable immune response
against SARS-CoV-2 VOCs in mice.
Previously, the researchers demonstrated that DCFHP alum remained stable at temperatures from 4°C to 37°C for at least 14 days, which was evaluated by mouse immunization studies
.
Therefore, the authors anticipate that local distribution of DCFHP alum vaccines is feasible
without refrigeration.

The article demonstrates that a two-dose intramuscular immunity regimen using DCFHP alum in rhesus monkeys yields durable, stable, and broadly neutralizing VOCs, including Omicron subvariants BA.
4/537 and BQ.
1,38, as well as balanced Th1 and Th2 immune responses
.
Notably, these non-human primate (NHP) antiserums also showed strong and durable neutralizing activity
against phylogenically distinct SARS-CoV-1 pseudoviruses.
After about 1 year, enhancing these immune-immune NHPs with a third dose of DCFHP alum yields a powerful, broad-spectrum, memory-neutralizing antibody response
.
Taken together, these results suggest that DCFHP alum may offer an affordable and effective solution for childhood and global SARS-CoV-2 vaccination and offer the potential for an effective, once-a-year booster dose
.

The author is the inventor of Stanford University and Chan Zuckerberg Biohub patenting immunogenic coronavirus fusion proteins and related methods, which have been licensed to Vaccine Inc.