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Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.

ABSTRACT: Using a gp120 envelope glycoprotein from the JR-FL strain of human immunodeficiency virus-1 (HIV-1) as a model antigen, the goal of the current study was to evaluate the level and quality of antibody responses elicited by different prime-boost vaccination regimens (protein only, DNA only, DNA plus protein) in rabbits. Our data demonstrated that incorporating DNA immunization as a prime in a heterologous prime-boost regimen was able to elicit a more diverse and conformational epitope profile, higher antibody avidity, and improved neutralizing activity than immunization with only protein. Additionally, this improved neutralizing activity was observed in spite of similar antibody specificities and avidities seen when only DNA vaccination was used, providing additional evidence that the use of a combination immunization regimen increases the protective antibody response. Insights gained from the current study confirmed that the heterologous DNA prime-protein boost approach is effective in eliciting not only high level but also improved quality of antigen-specific antibody responses, and thus may offer a new technology platform to develop better and safer subunit vaccines.

SUBMITTER: Vaine M

PROVIDER: S-EPMC2847033 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.

Vaine Michael M Wang Shixia S Hackett Anthony A Arthos James J Lu Shan S

Vaccine 20100217 17

Using a gp120 envelope glycoprotein from the JR-FL strain of human immunodeficiency virus-1 (HIV-1) as a model antigen, the goal of the current study was to evaluate the level and quality of antibody responses elicited by different prime-boost vaccination regimens (protein only, DNA only, DNA plus protein) in rabbits. Our data demonstrated that incorporating DNA immunization as a prime in a heterologous prime-boost regimen was able to elicit a more diverse and conformational epitope profile, hig ...[more]

PMID: 20170767

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Project description:BackgroundBooster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied.MethodsWe conducted a non-randomized, non-blinded phase II observational community trial acrossBahrain, investigating the reactogenic and immunogenic responseof participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological statuswas determined at baseline and on the following 8thweek. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling.Results305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study,with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred.ConclusionHeterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated. Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.

Dataset Information

Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.

Publications

Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.

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