In a recent study published in Science Translational Medicine, researchers explored the durability of immunity imparted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adjuvanted subunit vaccine against the Omicron variant.
Regardless of the effectiveness of the initial coronavirus disease 2019 (COVID-19) vaccines, additional vaccines are necessary for combating the current and emerging SARS-CoV-2 variants of concern (VOCs). This notion was based on the threat to global health posed by declining vaccine-triggered immunity and the appearance of SARS-CoV-2 VOCs like Omicron.
Available reports showed that the effectiveness of the highly efficient COVID-19 messenger ribonucleic acid (mRNA) vaccines decreases by 20 to 30% six months following a two-dose vaccine regimen. The immunity against Omicron, a VOC significantly resistant to vaccine-elicited antibodies, declined even more sharply, reaching 8.8%, following the receipt of the two doses of the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. While 40% of the global population has not yet received a complete vaccination, the declining vaccine potency necessitates a vaccine booster shot.
About the study
In the present work, researchers examined the longevity of immune reactions induced by a COVID-19 subunit nanoparticle vaccine. The vaccine was comprised of the SARS-CoV-2 ancestral strain (Wu) receptor binding domain (RBD) and was AS03 adjuvanted.
The team previously analyzed the protective efficacy and immunogenicity of the vaccine among nonhuman primates (NHPs). Further, the Korean Ministry of Food and Drug Safety recently approved the AS03-adjuvanted RBD-I53-50 for use in people aged 18 and older after meeting its primary endpoint in a phase III clinical study. Currently, the investigators assessed the duration of protective immunity following booster vaccination with RBD-β (RBD from the SARS-CoV-2 Beta variant) or RBD-Wu against the immune-elusive Omicron BA.1 variant.
The research involved four cohorts of male rhesus macaques. The initial group of five macaques received three doses of RBD-Wu + AS03 on days 0 and 21 and succeeded by a final booster shot about six months afterward, designated as group RBD-Wu/RBD-Wu/RBD-Wu.
The second and third cohorts were from the authors’ earlier research. Among these groups, two doses of RBD-Wu were given to one cohort of five animals, and two shots of HexaPro, i.e., the HexaPro spike (S) protein of the SARS-CoV-2 ancestral Wu strain expressed on the I53-50 nanoparticle, were given to the other group of six animals. During the prior investigation, both immunogens were delivered with the AS03 adjuvant on days 0 and 21 following a prime-boost protocol.
In the present research phase, almost one year following the initial vaccination series, all 11 animals from the second and third cohorts were booster vaccinated with an I53-50 nanoparticle immunogen expressing RBD-β proportionated with the Rpk9 mutations. Furthermore, the second group was designated as RBD-Wu/RBD-Wu/RBD-β and the third as HexaPro/HexaPro/RBD-β. Finally, the fourth cohort of five macaques was non-vaccinated controls.
According to the study results, the COVID-19 subunit vaccine containing the RBD of the SARS-CoV-2 ancestral strain (RBD-Wu) expressed on the I53-50 nanoparticle and AS03-adjuvanted provided NHPs with long-lasting protection against the Omicron BA.1 variant.
The authors noted that the vaccination-elicited neutralizing antibody (nAb) concentrations were retained at high levels for a minimum of one year following two-dose vaccination in these animals. In addition, it had a live virus nAb geometric mean titer (GMT) of 1331 and a pseudovirus nAb GMT of 1978 towards the SARS-CoV-2 ancestral strain yet not towards the Omicron BA.1 subvariant.
Nevertheless, a booster shot at six to 12 months using the RBD-β or RBD-Wu expressed on I53-50 induced prominent neutralizing titers targeting the Omicron and ancestral variants. In addition, the scientists found sustained neutralizing antibody titers towards a range of sarbecoviruses, like SARS-CoV.
Moreover, there were enduring and significant memory B and T cell reactions in response to Omicron and Beta VOCs. At six weeks following the last booster shot, vaccination provided immunity against Omicron infection across the lungs and reduced the viral burden inside the nares. The team noticed quick viral control in the nares and infection protection in the lungs even six months post-vaccination.
Collectively, the study data show that the COVID-19 AS03-adjuvanted RBD-I53-50 nanoparticle vaccine induces cross-protective and long-lasting immunity.
The study findings demonstrated that two doses of the COVID-19 subunit nanoparticle vaccine gave NHPs long-lasting but non-cross-reactive protection. Moreover, the team found that additional boosting with a vaccine version comprising the SARS-CoV-2 ancestral or the Beta variant RBD evoked cross-reactive immune reactions that provided the NHPs with immunity against Omicron challenge. These data imply that vaccines generated from diverse SARS-CoV-2 variants may induce cross-reactive immunity.