NVX-CoV2373-induced cellular and humoral immunity towards parental SARS-CoV-2 and VOCs compared to BNT162b2 and mRNA-1273-regimens

Hielscher, Franziska; Schmidt, Tina; Klemis, Verena; Wilhelm, Alexander; Marx, Stefanie; Abu‐Omar, Amina; Ziegler, Laura; Guckelmus, Candida; Urschel, Rebecca; Sester, Urban; Widera, Marek; Sester, Martina

doi:10.1016/j.jcv.2022.105321

Cited by 26 publications

(32 citation statements)

References 39 publications

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“…The NVX-CoV2373 subunit vaccine was also tested for a 2-dose vaccination schedule, eliciting lower IgG levels compared to the BNT162b2 and mRNA-1273 mRNA vaccines and a poor induction of spike-specific CD8 + T-cells. 33,34 These data contrast with those reported in the present study for PHH-1V. However, the NVX-CoV2373 induced spike-specific CD4 + T-cells to all tested VOCs (Wuhan-Hu-1, Alpha, Beta, Delta and Omicron BA.1 and BA.2).…”

Section: Discussioncontrasting

confidence: 99%

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Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

Corominas

Garriga

Prenafeta

et al. 2022

Preprint

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SummaryBackgroundA SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14 and 98 days after vaccine administration.MethodsThe HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine – either heterologous (PHH-1V group) or homologous (BNT162b2 group) – in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies against the ancestral Wuhan-Hu-1 strain and different variants of SARS-CoV-2 after the PHH-1V or the BNT162b2 boost, the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides and the safety and tolerability of PHH-1V as a boost. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553.FindingsFrom 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1·68 (p<0·0001) and 0·87 (p=0·43) for the ancestral Wuhan-Hu-1 strain; 0·61 (p<0·0001) and 0·57 (p=0·0064) for the beta variant; 1·01 (p=0·89) and 0·52 (p=0·0003) for the delta variant; and 0·59 (p=<0·0001) and 0·56 (p=0·0026) for the omicron variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89·3%) in the PHH-1V and 238 (94·4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79·7% and 89·3%), fatigue (27·5% and 42·1%) and headache (31·2 and 40·1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10·14%) for the PHH-1V group and 30 (11·90%) for the BNT162b2 group (p=0·45), and none of the subjects developed severe COVID-19.InterpretationOur interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, elicits a strong and sustained neutralizing antibody response against Wuhan-Hu-1 strain, and a superior one concerning the previous circulating beta and delta SARS-CoV-2 variants, as well as the currently circulating omicron. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe.FundingHIPRA SCIENTIFIC, S.L.U.

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Section: Discussioncontrasting

confidence: 99%

“…However, the NVX-CoV2373 induced spike-specific CD4 + T-cells to all tested VOCs (Wuhan-Hu-1, Alpha, Beta, Delta and Omicron BA.1 and BA.2). 34 The CoVLP-AS03, CoV2 preS dTM-AS03, and NVX-CoV2373 vaccines are now also being considered as booster doses for primary vaccination schedules.…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

Corominas

Garriga

Prenafeta

et al. 2022

Preprint

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“…The durability of the immune response following other vaccinations has largely been commensurate with antibody levels. 9 Nearly equivalent antibody responses between Novavax NVX-CoV2373/ TAK-019 and mRNA vaccination 59 imply that suppression of infection with the NVX-CoV2373/TAK-019 vaccine could be similar to that indicated for mRNA vaccines. Regardless of vaccine type, the efficacy of boosting will also depend on an individual's immune status.…”

Section: Discussionmentioning

confidence: 99%

Infection by SARS‐CoV‐2 with alternate frequencies of mRNA vaccine boosting

Townsend

Hassler

Dornburg

2023

Journal of Medical Virology

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One of the most consequential unknowns of the COVID‐19 pandemic is the frequency at which vaccine boosting provides sufficient protection from infection. We quantified the statistical likelihood of breakthrough infections over time following different boosting schedules with messenger RNA (mRNA)‐1273 (Moderna) and BNT162b2 (Pfizer‐BioNTech). We integrated anti‐Spike IgG antibody optical densities with profiles of the waning of antibodies and corresponding probabilities of infection associated with coronavirus endemic transmission. Projecting antibody levels over time given boosting every 6 months, 1, 1.5, 2, or 3 years yielded respective probabilities of fending off infection over a 6‐year span of >93%, 75%, 55%, 40%, and 24% (mRNA‐1273) and >89%, 69%, 49%, 36%, and 23% (BNT162b2). Delaying the administration of updated boosters has bleak repercussions. It increases the probability of individual infection by SARS‐CoV‐2, and correspondingly, ongoing disease spread, prevalence, morbidity, hospitalization, and mortality. Instituting regular, population‐wide booster vaccination updated to predominant variants has the potential to substantially forestall—and with global, widespread uptake, eliminate—COVID‐19.

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“…Finally, the immune tests used in our study may have failed to detect SARS-CoV-2 specific immune responses. However, we have used either commercial assays or in-house assays that have been extensively evaluated for characterization of the development of SARS-CoV-2 specific T cells after infection and COVID-19 vaccination [ 10 , 11 , 12 , 13 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Transient Positive SARS-CoV-2 PCR without Induction of Systemic Immune Responses

et al. 2023

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SARS-CoV-2 testing is dominated by PCR to guide treatment and individual as well as public health preventive measures. Among 1700 football (soccer) players and staff of the German Bundesliga and Bundesliga 2 who were regularly tested by PCR twice weekly, 98 individuals had a positive PCR (May 2020 to mid-January 2021). A subset of these were retested shortly after the initial positive result. Among those, 11 subjects were identified who only had a transient single positive PCR of low viral load. All individuals were asymptomatic and none developed long COVID. We tested SARS-CoV-2 IgG and IgA as well as SARS-CoV-2 specific CD4 und CD8 positive T cells, and showed that only one out of 11 individuals developed SARS-CoV-2 specific cellular and humoral immunity after the positive PCR, whereas a specific immunity was undetectable in all other individuals. Thus, a single positive PCR might indicate that transient colonization of the upper respiratory tract with SARS-CoV-2 may occur without systemic induction of specific adaptive immunity. Together with test artifacts as another potential reason for a transiently positive test, this finding may favor cautious interpretation of positive PCR results or retesting before initiating intervening treatment or infection control measures in some cases.

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NVX-CoV2373-induced cellular and humoral immunity towards parental SARS-CoV-2 and VOCs compared to BNT162b2 and mRNA-1273-regimens

Cited by 26 publications

References 39 publications

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

Infection by SARS‐CoV‐2 with alternate frequencies of mRNA vaccine boosting

Transient Positive SARS-CoV-2 PCR without Induction of Systemic Immune Responses

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