Zifivax (ZF2001) COVID-19 Vaccine Description For 2022

Anhui Zhifei Longcom ZifiVax ZF2001 (ZF-UZ-VAC-2001) is a protein subunit vaccine using a dimeric form of the receptor-binding domain (RBD) as the antigen, a harmless piece of the SARS-Cov-2 virus. The ZF2001 recombined vaccine encodes the SARS-CoV-2 RBD antigen (residues 319–537, accession number YP_009724390), with two copies in tandem repeat dimeric form, and was manufactured in the CHOZN CHO K1 cell line (Sigma-Aldrich Trading; Shanghai, China) as a liquid formulation containing 25 μg or 50 μg per 0·5 mL in a vial, with aluminum hydroxide as the adjuvant.

The New England Journal of Medicine published an Original Article on May 4, 2022, that reported in a large cohort of adults in a phase 3 study, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least six months after complete vaccination. In addition, on March 1, 2022, a non-peer-reviewed, randomized, observer-blinded, placebo-controlled phase 4 clinical trial in healthy adults reported heterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating with viral vector vaccines and recombinant protein vaccines.  

Previously, researchers found that vaccination with the ZF2001 25 or 50 μg doses and two-dose or three-dose schedules was a well-tolerated phase 1/2 studies, and most adverse events were mild or moderate, with the most common being injection-site pain, redness, and swelling.

As of December 2022, ZifiVax has conducted six phase 3 clinical trials and has received authorization in China, Columbia, Indonesia, and Uzbekistan. In addition, ZF2001 requires less stringent cold-chain transport and storage, a factor that facilitates its availability in the global supply. 

The vaccine was jointly developed by the Institute of Microbiology, the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical. The vaccine was manufactured according to good manufacturing practice guidelines by Anhui Zhifei Longcom Biopharmaceutical. DrugBank Accession Number: DB15893. This vaccine may also be referred to as RBD-Dimer, Zifivax.

Zifivax (ZF2001) Indication

ZF2001 COVID-19 Vaccine is indicated to prevent COVID-19 severe disease from the SARS-CoV-2 virus. The three-dose ZF2001 regimen had a vaccine efficacy against Covid-19 of any severity of 81.4% in the short-term follow-up and 75.7% in the long-term follow-up. The waning of efficacy was small (Table S12). Therefore, with an efficacy of more than 75% and a lower boundary of the 95% confidence interval of more than 30%, this vaccine met our prespecified criteria for success and exceeded the preferred criteria (≥70%) of WHO Target Product Profiles for Covid-19 vaccines.30 Vaccine efficacy against the severe-to-critical disease was 92.9% in the short-term follow-up and 87.6% in the long-term follow-up. Therefore, ZF2001 would provide fundamental immunity.

Zifivax (ZF2001) Effectiveness Against Virus Variants

As reported on May 4, 2022, in serum samples, the majority of vaccine-elicited neutralizing activities against the B.1.351 (beta) variant of concern and pseudovirus expressing a panel of spikes from variants of concern and variants of interest, including B.1.1.7 (alpha), beta, delta, B.1.617.1 (kappa), and omicron, were shown to be preserved. 

Media reported in August 2021; that a Phase III trial showed ZF 2001 had an efficacy of 93% against the Alpha variant and 78% efficacy against the Delta variant. And in July 2021, lab studies showed ZF2001 retained neutralizing effects against B.1.429, B.1.351, P.1, B.1.525, B.1.617.1; the neutralizing titers decreased from 1.1 fold to 2.1 fold. In February 2021, lab studies of twelve serum samples taken from recipients of ZF2001 retained neutralizing activity against the Beta variant, although with weaker activity than against the original virus.

Zifivax (ZF2001) Dosage

The safety and immunogenicity data from the phase 1 and 2 trials support using the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy. And the participants with an extended interval between the second and third doses (doses at 0, 1, and 4–6 months) showed higher neutralizing activity and resilience to variants than those with shorter intervals (doses at 0, 1, and 2 months; appendix pp 5–6), which is consistent with the previous study of neutralization of the SARS-CoV-2 beta variant by ZF2001-elicited antisera. The better performance data of the extended interval regimen is probably because of the longer antibody maturation in the recipients than in those with the shorter interval regimen.

Zifivax (ZF2001) Side effects

In the phase 1 trial, six (60%) of ten participants in the placebo group, 14 (70%) of 20 in the 25 μg group, and 18 (90%) of 20 in the 50 μg group reported at least one adverse event within 30 days after vaccination, with no significant between-group differences. In the phase 2 trial, the overall frequency of adverse events was low within 30 days after vaccination.

Zifivax (ZF2001) News For 2021 - 2022

November 30, 2022 - Local media reported the Jakarta Health Office had expanded coverage for the third and fourth doses of COVID-19 vaccination.

November 21, 2022 - ANTARA reported the Jakarta Health Office had distributed 49,000 doses of the Zifivax vaccine to 44 public health centers in the capital city.

May 4, 2022 - The peer-review journal NEJM published an Original Article that concluded, 'ZF2001 provides clinical evidence that an RBD-based vaccine is a promising alternative in the prevention of symptomatic Covid-19.'

February 21, 2022 - China began delivering COVID-19 booster shots based on technologies different from those used in initial inoculations, including the protein subunit COVID-19 vaccine made by Anhui Zhifei Longcom Biopharmaceutical.

January 10, 2022 - The AP reported that Indonesian authorities granted emergency authorization for the use of five different COVID-19 vaccines as booster shots that will prioritize vulnerable groups. Penny Lukito, head of Indonesia's Food and Drug Monitoring Agency, said the Zifivax vaccine would be distributed as a third vaccine shot in the country.

October 8, 2021 - Indonesia's drug and food authority BPOM confirmed it had issued an emergency use authorization for the Zifivax COVID-19 vaccine produced by Anhui Zhifei Longcom.

August 20, 2021 - The Lancet published - Neutralisation of ZF2001-elicited antisera to SARS-CoV-2 variants. We provide preliminary evidence of the approved RBD-based protein subunit vaccine for its neutralization profile to SARS-CoV-2 variants. The high susceptibility of these new variants to the ZF2001 vaccine supports the method of mass immunization to build herd immunity. However, the vaccine effectiveness against these variants must be validated by phase 3 clinical trials and real-world data.

June 30, 2021 - Uzbekistan has received 2 million doses of the Zifivax vaccine, developed by Anhui Zhifei Longcom in collaboration with the Institute of Microbiology at the Chinese Academy of Sciences, have arrived in the capital Tashkent, the ministry said.

March 24, 2021 - The Lancet published 'Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomized, double-blind, placebo-controlled, phase 1 and 2 trials.' Study Interpretation: The protein subunit vaccine ZF2001 appears to be well-tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support using the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy.

March 16, 2021 - Gao Fu, the head of China's CDC, led the development of a protein subunit vaccine approved by regulators last week for emergency use, the Chinese Academy of Sciences' Institute of Microbiology said in a statement.

February 14, 2021 - Anhui Zhifei Longcom Biopharmaceutical Co., Ltd, together with the government of Uzbekistan, will jointly work on the approval of emergency usage authorization (EUA) and marketing authorization (MA) of the ZF2001 vaccine in the Republic of Uzbekistan for the prevention and control of the COVID-19 in the country, to achieve the public health goals of Uzbekistan. With EUA and MA approval, the ZF2001 vaccine will be distributed in the Republic of Uzbekistan under ZF-UZ-Vac2001.

February 2, 2021 - A non-peer-review study reported Encouragingly that both 31 vaccines largely preserved neutralizing titers, with a slight reduction, against 501Y.V2 32 authentic viruses compared to their titers against both original SARS-CoV-2 and the currently 33 circulating D614G virus. These data indicated that the 501Y.V2 variant would not escape the 34 immunity induced by vaccines targeting the whole virus or RBD.

Zifivax (ZF2001) COVID-19 Vaccine Clinical Trials

Various clinical trials are listed here.

A Phase 3 clinical trial Determined the Safety and Efficacy of ZF2001, a Recombinant Novel Coronavirus Vaccine (CHO Cell) for the Prevention of COVID-19. ClinicalTrials.gov Identifier: NCT04646590 - A Phase III Clinical Trial to Determine the Safety and Efficacy of ZF2001 for Prevention of COVID-19.