Effects of Influenza Vaccination on the Response to BNT162b2 Messenger RNA COVID-19 Vaccine in Healthcare Workers

Abstract

Background: Vaccine-induced immunity is at present the main strategy to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent evidences suggested a protective effect of influenza vaccination against coronavirus disease 2019 (COVID-19) severity, while impact on the immune response to BNT162b2 messenger RNA (mRNA) vaccine is under investigation.

Methods: We aimed to evaluate this aspect in a cohort of 297 healthcare workers (108 males, 189 females) after seasonal influenza vaccination compared to no-flu-vaccination. VAX+ (165 individuals; 63 males and 102 females) had tetravalent influenza vaccine, and VAX- (132 individuals; 45 males and 87 females) had no flu vaccination. Anti-spike-receptor binding domain (RBD) level was tested 15 - 70 days after BNT162b2 second inoculum.

Results: Increased antibody response was observed in total VAX+ compared to VAX- (2,047.4 vs. 1,494.2 binding antibody unit (BAU)/mL, P = 0.0039), independently from gender and body mass index (BMI). Younger total individuals (< 35 years) showed significant increase of the level of binding antibodies (2,184.8 vs. 1,590.9 BAU/mL, P = 0.0038) compared to ≥ 35 years; young/old difference was lost restricting to VAX+ subgroup. Flu vaccinations appear associated to better antibody response in older individuals (P = 0.027, ≥ 35 years VAX+ vs. VAX-). A decreasing trend during time was observed for both VAX+ and VAX-, except for < 35 years VAX- individuals. Early response was higher in VAX+ compared to VAX-; however a more rapid waning was observed in VAX+ subjects.

Conclusions: Our data showed better antibody response to SARS-CoV-2 vaccine in subjects already vaccinated against seasonal influenza; this may represent one of the mechanisms underlying the cross-protective effects of influenza vaccination against heterologous infections reported in recent epidemiological studies.

Keywords: BNT162b2 mRNA vaccine; Influenza vaccination; SARS-CoV-2; Vaccine-induced immunity.

Figure 1

Correlation of total antibodies to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) and body mass index (BMI) after complete BNT162b2 vaccination in (a), all analyzed HCWs (males and females) vaccinated for seasonal influenza (VAX+) compared to not vaccinated for seasonal influenza (VAX-), the black dotted trend line indicates regression between all analyzed subjects; and in (b), VAX+ and (c), VAX- individuals. Simple regression analysis with P = 0.054 and 0.484 for total males and females, respectively (a); P = 0.356 and 0.560 for VAX- males/females (b); P = 0.148 and 0.973 for VAX+ males/females (c). SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; HCWs: healthcare workers; BAU: binding antibody unit.

Figure 2

Total antibodies to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) response after complete BNT162b2 vaccination in individuals < 35 years old, vaccinated for seasonal influenza (VAX+) and not vaccinated (VAX-), and individuals ≥ 35 years old, vaccinated for seasonal influenza (VAX+) and not vaccinated (VAX-). Asterisks indicate statistical significance (*P < 0.05). SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; BAU: binding antibody unit.

Figure 3

Serum level of total antibodies anti SARS-CoV-2 spike receptor binding domain (RBD) during time after complete BNT162b2 vaccination 15 - 70 days after second dose) in (a) individuals vaccinated for seasonal influenza (VAX+) < 35 and ≥ 35 years old, simple regression analysis with P = 0.001 and 0.0004, respectively; (b) individuals not vaccinated (VAX-) < 35 and ≥ 35 years old, simple regression analysis with P = 0.0003 and 0.003, respectively; and (c) earlier and later immune response, measured within 20 days from complete BNT162b2 vaccination and after 30 - 70days. Asterisks indicate statistical significance (*P < 0.05; **P < 0.01). BAU: binding antibody unit.