SARS-CoV-2 S1 Subunit Booster Vaccination Elicits Robust Humoral Immune Responses in Aged Mice

Abstract

Currently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death of the disease. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants raises concerns of reduced vaccine effectiveness and increased risk of infection. Repeated homologous booster in elderly individuals and immunocompromised patients is considered to solve severe form of disease caused by new SARS-CoV-2 variants but cannot protect completely against breakthrough infection. In our previous study we assessed the immunogenicity of an adenovirus-based vaccine expressing SARS-CoV-2-S1 (Ad5.S1) in mice, resulting in that a single immunization with Ad5.S1, via subcutaneously injection or intranasal delivery, induced robust humoral and cellular immune responses. As a follow up study, here we showed that vaccinated mice had high titers of anti-S1 antibodies at one year after vaccination compared to PBS immunized mice. Furthermore, one booster dose of non-adjuvanted recombinant S1Beta (rS1Beta) subunit vaccine was effective in stimulating strong long-lived S1-specific immune responses and inducing significantly high neutralizing antibodies against the Wuhan, Beta, and Delta strain with 3.6- to 19.5-fold change increases. Importantly, the booster dose elicits cross-reactive antibody responses resulting in ACE2 binding inhibition against spike of SARS-CoV-2 variants (Wuhan, Alpha, Beta, Gamma, Delta, Zeta, Kappa, New York, India) as early as two-week post-boost injection, persisting over 28 weeks after a booster vaccination. Interestingly, levels of neutralizing antibodies were correlated with not only level of S1-binding IgG but also level of ACE2 inhibition in the before- and after-booster serum samples. Our findings show that S1 recombinant protein subunit vaccine candidate as a booster has potential to offer cross-neutralization against broad variants, and has important implications for vaccine control of new emerging breakthrough SARS-CoV-2 variants in elderly individuals primed with adenovirus-based vaccine like AZD1222 and Ad26.COV2.S.

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

“…Protein subunit vaccine approaches against COVID-19 are highly favorable for worldwide equitable distribution due to their low cost per dose, relative thermostability, and excellent safety profile [ 22 , 23 , 24 , 25 ]. Our previously published reports on vaccines against SARS-CoV-1, Middle-East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 have demonstrated the ability of S1 subunit targeting vaccines to generate neutralizing antibody responses against Beta coronaviruses [ 26 , 27 , 28 , 29 , 30 ].…”

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

“…The copyright holder for this preprint this version posted December 14, 2022. ; https://doi.org/10.1101/2022.12.12.520124 doi: bioRxiv preprint chose to focus on the induction of antibodies because they are the hypothesized correlate of protection against severe COVID-19 20 . Furthermore, prior studies have shown the positive correlation and high concordance between binding antibodies and traditional virus-based microneutralization tests 30 . Our past work has also shown the positive correlation between the MSD ACE2 binding inhibition and virus-based microneutralization tests 30 .…”

“…Furthermore, prior studies have shown the positive correlation and high concordance between binding antibodies and traditional virus-based microneutralization tests 30 . Our past work has also shown the positive correlation between the MSD ACE2 binding inhibition and virus-based microneutralization tests 30 . As a conventional and multiplex test, measurement of competitive immunoassay for quantifying inhibition of the spike-ACE2 interaction can serve as a surrogate for traditional virus-based microneutralization tests with high levels of correlation 41,44,63 .…”

“…Indeed, BALB/c mice are the prototypical Th2-type mouse strain which necessitates the investigation of this protein subunit vaccine in additional animal models to examine the risk of vaccine-associate enhanced respiratory disease (VAERD) 55 . Our previous research has suggested that a booster of unadjuvanted subunit vaccine after an Adenoviral prime vaccine might avoid Th2-based immune response and the occurrence of VAERD 30 . Indeed, there have been numerous Adenoviral vector vaccine platforms used in the SARS-CoV-2 pandemic and constitute a large population necessitating variant-specific boosting 7,56 .…”

“…Protein subunit vaccine approaches against COVID-19 are highly favorable for worldwide equitable distribution due to their low cost per dose, relative thermostability, and excellent safety profile [22][23][24][25] . Our previously published reports on vaccines against SARS-CoV-1, Middle-East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 have demonstrated the ability of S1 subunit targeting vaccines to generate neutralizing antibody responses against Beta coronaviruses [26][27][28][29][30] .…”