Heterologous third and fourth doses of the BNT162b2 vaccine significantly increases COVID-19 immunogenicity among individuals who had suboptimal immune responses following an initial priming series with the CVnCOV vaccine, according to results of a study published in eClinicalMedicine.

This prospective controlled cohort study was conducted at 3 centers in Spain between July and September 2021. Patients included were those who received 2 priming doses of the experimental CVnCOV COVID-19 vaccine and had suboptimal immune responses. The researchers sought to determine the effects of heterologous BNT162b2 COVID-19 vaccination among patients who had suboptimal immune responses following receipt of 2 priming doses of the experimental CVnCOV vaccine. Immunogenicity was evaluated after administration of a third and fourth dose of the BNT162b2 vaccine. The analysis also included a control group, comprising patients who had not been primed with any type of COVID-19 vaccine. Patients in the control group were administered 2 doses of the BNT162b2 COVID-19 vaccine. Immune responses were compared between the 2 patient groups, as well as neutralizing antibody levels and reactogenicity.

Among patients in the intervention (n=92) and control (n=38) groups included in the final analysis, the median age was 27 (IQR, 23-45) and 26 (IQR, 24-28) years, and 39% and 33% were women. In both groups, less than 5% of patients had comorbidities. Of patients in the intervention group, the median time between receipt of the second and third vaccine doses was 110 days.


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After receipt of first BNT162b2 vaccine dose,  stronger humoral immune responses, measured via anti-receptor binding domain (RBD) antibodies, were observed among patients in the intervention group vs those in the control group (median, 10,740.0 vs 29.8 binding antibody units [BAU]/mL; P <.0001). Half-maximal neutralization titers (NT50) against the G614 SARS-COV-2 spike variant were also compared between the 2 patient groups after administration of the first BNT162b2 dose. Results showed that NT50 values were increased among patients in the intervention group vs those in the control group (median, 2674.0 vs 63.0; P <.0001), with geometric mean titers of 2659.8 vs 65.6, respectively.

After receipt of the second BNT162b2 vaccine dose, anti-RBD antibody titers were also significantly increased among patients in the intervention group vs those in the control group (median, ≥12,500 vs 1859.0 BAU/mL; P <.0001), with similar findings in regard to NT50 values (median, 2626.5 vs 850.4; P <.0001).

The highest (≥12,500 BAU/mL) level of measurable anti-RBD antibodies among the intervention group was detected in 42.4% and 70.9% of patients after receipt of the first BNT162b2 dose and between 2 to 5 weeks after receipt of the second BNT162b2 dose, respectively

Neutralizing capacity against the G614, Delta, Beta, Mu, and Omicron SARS-CoV-2 variants was increased among patients in the intervention group vs those in the control group after receipt of both the first and second doses of the BNT162b2 vaccine.

Reactogenicity trends were similar among both patient groups, with headache and myalgia as the most commonly reported systemic reactions. No severe adverse events were reported.

This study was limited by the lack of a third BNT16b2 vaccine dose among patients in the control group.

According the researchers, “further studies on immunogenicity and efficacy of booster and extra doses of COVID-19 vaccines are warranted to better understand immune response against SARS-COV-2 infection…”

Disclosure: Multiple authors declared affiliations with industry. Please see the original article for a full list of disclosures.

Reference

Ascaso-del-Rio A, García-Pérez J, Pérez-Olmeda M, et al. Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study. EClinicalMedicine. 2022;51:101542. doi:10.1016/j.eclinm.2022.101542