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Boosting with Multiple Doses of mRNA Vaccine after Priming with Two Doses of Protein Subunit Vaccine MVC-COV1901 Elicited Robust Humoral and Cellular Immune Responses against Emerging SARS-CoV-2 Variants.
Chiu, Chun-Hsiang; Chang, Yu-Hsiu; Tao, Chi-Wei; Chang, Feng-Yee; Chiu, Kuo-Chou; Chang, Tien-Wei; Yen, Li-Chen.
  • Chiu CH; Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospitalgrid.278244.f, National Defense Medical Centergrid.260565.2, Taipei, Taiwan.
  • Chang YH; Institute of Preventive Medicine, National Defense Medical Centergrid.260565.2, Taipei, Taiwan.
  • Tao CW; Division of Chest Medicine, Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan.
  • Chang FY; Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospitalgrid.278244.f, National Defense Medical Centergrid.260565.2, Taipei, Taiwan.
  • Chiu KC; Department of Family Dentistry, Tri-Service General Hospitalgrid.278244.f, National Defense Medical Centergrid.260565.2, Taipei, Taiwan.
  • Chang TW; School of Dentistry, National Defense Medical Centergrid.260565.2, Taipei, Taiwan.
  • Yen LC; Department of Microbiology and Immunology, National Defense Medical Centergrid.260565.2, Taipei, Taiwan.
Microbiol Spectr ; 10(5): e0060922, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2019759
ABSTRACT
Confronted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as Delta and Omicron, with high infectivity and immune evasion capacity, vaccination remains the most effective tool to prevent infection and severe illness. However, heterologous vaccination of mRNA vaccines primed with protein subunit vaccines had not been evaluated before the current study. Since subunit vaccine MVC-COV1901 (MVC) has been granted emergency use authorization in Taiwan, in this study, we explored the humoral and cellular immune responses to additional third (2× MVC/Mod) and fourth (2× MVC/2× Mod) doses of mRNA-1273 (Mod) after priming with two doses of subunit vaccine MVC against the emerging variants. We found a 12.3- to 16.1-fold increase in antibodies targeting the receptor binding domain (RBD) of the Delta variant with 2× MVC/Mod compared to two doses of MVC (2× MVC) or AZD1222 (2× AZ) regimens and a 26- to 32.2-fold improvement in neutralizing potency against the Omicron variant (BA.1). Besides, the numbers of gamma interferon (IFN-γ)-secreting T cells induced by 2× MVC/Mod were also elevated 3.5-fold and 3.7- to 4.3-fold for the wild type and Delta variant. However, boosting with a fourth dose of Mod (2× MVC/2× Mod) after the 2× MVC/Mod regimen failed to significantly improve the immune responses. Moreover, all vaccination schedules showed reduced neutralizing activity against the Omicron variant. Collectively, our results suggested that the third or fourth dose booster vaccination with mRNA vaccine after priming with two doses of protein subunit vaccine could elicit stronger humoral and cellular immune responses. These findings could provide a future global heterologous boosting strategy against COVID-19. IMPORTANCE Vaccination is the most important strategy to combat the COVID-19 outbreak; however, it remains to be determined whether heterologous prime-boost regimens could induce equal or even stronger immune responses against SARS-CoV-2. Here, we showed that boosting the additional doses of mRNA-1273 (Mod) priming with two doses of MVC-COV1901 (MVC) (2× MVC/Mod) improved humoral and cellular immunity compared to two doses of AZD1222 (2× AZ) or MVC (2× MVC) against SARS-CoV-2 variants. However, the Omicron variant showed strong immune evasion ability for all vaccination schedules. Our findings provided evidence supporting that heterologous vaccination by boosting with mRNA vaccine after priming with two doses of protein subunit vaccine could strongly promote humoral and cellular immune responses against the emerging SARS-CoV-2 variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / COVID-19 Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Humans Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.00609-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / COVID-19 Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Humans Language: English Journal: Microbiol Spectr Year: 2022 Document Type: Article Affiliation country: Spectrum.00609-22