Immunogenicity and safety of the protein-based heterodimer booster vaccine for COVID-19

In a recent study posted to the medRxiv* preprint server researchers compared the immunogenicity and safety of the protein-based heterodimer vaccine (PHH-1V) and BNT162b2 coronavirus disease 2019 (COVID-19) vaccines.

Background

A vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) called PHH-1V has been tested to be well tolerated and safe in young, healthy adults. Further research is needed to understand the efficacy of PHH-1V against COVID-19.

About the study

In the present study, researchers reported the immunogenicity and safety of a COVID-19 PHH-1V heterologous booster compared to a BNT162b2 homologous booster 14 and 98 days after COVID-19 vaccination.

This non-inferiority and double-blind phase IIb study assessed the safety and immunogenicity of PHH-1V and was conducted in 10 centers in Spain. Eligible subjects were 18 years of age and older and had a history of two doses of the BNT162b2 COVID-19 vaccine between 182 and 365 days after the second vaccine dose. The eligible participants also had a body-mass index (BMI) of 18 to 40 kg/m²were polymerase chain reaction (PCR) negative for SARS-CoV-2 at the time of study enrollment, and were willing to avoid vaccinations with other vaccines four weeks before or after the COVID-19 vaccination.

The team randomly assigned participants in a 2:1 ratio to administer a third vaccine dose with either the BNT162b2 vaccine or the PHH-1V vaccine. The participants were also assigned for interactive response technology (IRT) treatment. The team categorized the assignment order according to the age group of the participants, with 90% of subjects in the cohort aged 18 to 64 and 10% in the cohort aged 65 and older.

Study visits were set at days zero, 14, 28, and at three, six, and 12 months for eligible participants vaccinated at the day zero visit. The participants were vaccinated with BNT162b2 and PHH-1V. The team observed the first 30 subjects for 60 minutes, followed by telephone surveillance for the next 72 hours. The rest of the participants were followed for 30 minutes, followed by telephone contact on day 7.

The antibody neutralization (NAb) titers were tested with the inhibitory concentration 50 (IC₅₀) by a pseudovirion-based neutralization assay (PBNA). In addition, immunogenicity against the viral peak glycoprotein was analyzed using the anti-SARS-CoV-2 spike immunoassay. An infectious SARS-CoV-2 neutralization assay (VNA) was also used to assess the NAb titers estimated as inhibitory dilution 50 (ID₅₀† Further Geometric Mean Fold Rise (GMFR) and Geometric Mean titre (GMT) were estimated for each parameter.

Results

A total of 862 subjects were screened, including 522 adults who received PHH-1V and 260 received a booster vaccine dose of BNT162b2. In addition, the modified intention-to-treat (mITT) cohort included 504 PHH-1V and 248 BNT162b2, and the safety protocol (SP) cohort had 513 PHH-1V and 252 BNT162b2, and the immunogenicity population (IGP) had 503 PHH-1V and 246 BNT162b2 participants.

The team noted that for the SARS-CoV-2 Wuhan strain, the GMT on day 14 was 3357.50 for the BNT162b2 group and 1998.95 for the PPH-1V group and had a GMT ratio of 1.68 . On the other hand, the GMT ratio at day 98 was 0.87, indicating non-inferiority of the vaccine response corresponding to PHH-1V to BNT162b2. In addition, the GMT for the SARS-CoV-2 beta variant from day 14 was 2658.04 for the BNT162b2 group and 4328.93 for the PPH-1V group and had a GMT ratio of 0.61, indicating suggested that PHH-1V was superior to BNT162b2. At day 98 for the beta variant, 0.57 was the GMT ratio, confirming the superiority of PHH-1V for beta.

The team also noted that the GMT for the SARS-CoV-2 Delta variant from day 14 was 1487.13 for the BNT162b2 group and 1471.60 for the PPH-1V group and a GMT ratio of 1.01 suggesting PHH-1V non-inferiority to BNT162b2. At day 98 for the Delta variant, the GMT ratio was 0.52, indicating PHH-1V superiority for the Delta variant. The team also found that the GMT for the SARS-CoV-2 Omicron variant from day 14 was 1219.08 for the BNT162b2 group and 2053.73 for the PPH-1V group and had a GMT ratio of 0.59 , indicating PHH-1V superiority over BNT162b2 for the Omicron variant. At day 98 for the Omicron variant, the GMT ratio was 0.56, further confirming the superiority of PHH-1V to Omicron.

The study also found that 89.3% and 94.4% of participants who belonged to the PHH-1V and BNT162b2 groups reported at least one adverse event, including mild symptoms in 66.7% of the PHH-1V and 57.9% of the BNT162b2 cohorts. The most frequently experienced adverse reactions were injection site pain, fatigue and headache in the PHH-1V and BNT162b2 groups.

Conclusion

Overall, the study results showed that the PHH-1V vaccine was well tolerated and safe for treating COVID-19, while also stimulating a robust neutralizing antibody response against the viral variants tested.

*Important announcement

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