The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection

Arieta, Christina M.; Xie, Yushu Joy; Rothenberg, Daniel; Diao, Huitian; Harjanto, Dewi; Meda, Shirisha; Marquart, Krisann; Koenitzer, Byron; Sciuto, Tracey E.; Lobo, Alexander; Zuiani, Adam; Krumm, Stefanie A.; Couto, Carla Iris Cadima; Hein, Stephanie; Heinen, André; Ziegenhals, Thomas; Liu-Lupo, Yunpeng; Vogel, Annette B.; Srouji, John R.; Fesser, Stephanie; Thanki, Kaushik; Walzer, Kerstin C; Addona, Theresa A.; Türeci, Özlem; Şahin, Uğur; Gaynor, Richard B.; Poran, Asaf

doi:10.1016/j.cell.2023.04.007

Cited by 36 publications

(26 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early studies of infection of humans with 229-E, an alphacoronavirus and common cause of colds, showed that antibody titers were inversely related to symptomatic illness but that some individuals with very low antibody titers still did not present with symptomatic illness. 20 SARS-CoV-2 hamster challenge studies have revealed that T-cell mediated responses can protect against severe illness even in the absence of spike-specific antibody responses, 21 and our findings suggest a likely role for T cells in preventing illness in humans, even under circumstances of considerable viral antigenic variation. This possibility is currently under investigation by our group.…”

Section: Discussionsupporting

confidence: 57%

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Bates,

Lirette,

Farmer

et al. 2024

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

show abstract

Section: Discussionsupporting

confidence: 57%

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Bates,

Lirette,

Farmer

et al. 2024

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

show abstract

“…However, the data presented here may be additionally clarifying because they demonstrate the potential beneficial effect of SARS-CoV-2–specific CD8 + T cells in the absence of any detectable anti-spike protein antibodies, which could be of additional benefit, given that T cell responses have been demonstrated to have enhanced durability in comparison with antibodies ( 33 – 35 ). This suggests that efforts to develop dedicated SARS-CoV-2 CD8 + T cell–based vaccines ( 36 , 37 ) to augment existing spike protein-based vaccines could be of substantial benefit for both B cell–deficient individuals and the population at large.…”

Section: Discussionmentioning

confidence: 99%

T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19

Zonozi,

Walters,

Shulkin

et al. 2023

Sci. Transl. Med.

View full text Add to dashboard Cite

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4 + and CD8 + T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell–deficient individuals, particularly within the CD8 + T cell compartment, in comparison with healthy controls. Evaluation of clinical outcomes demonstrates that vaccination of RTX-treated individuals was associated with about 4.8-fold reduced odds of moderate or severe COVID-19 in the absence of vaccine-induced antibodies. Analysis of T cell differentiation demonstrates that RTX administration increases the relative frequency of naïve CD8 + T cells, potentially by depletion of CD8 + CD20 dim T cells, which are primarily of an effector memory or terminal effector memory (TEMRA) phenotype. However, this also leads to a reduction in preexisting antiviral T cell immunity. Collectively, these data indicate that individuals with B cell deficiencies have enhanced T cell immunity after both SARS-CoV-2 infection and vaccination that potentially accounts for reduced hospitalization and severe disease from subsequent SARS-CoV-2 infection.

show abstract

“…The proportion of BA.2.86 and closely related descendent lineages, such as JN.1, characterized by an additional substitution of L455S in the Spike protein, is currently steadily increasing, indicating high transmission fitness and efficient humoral immune evasion [ 107 ]. However, T cell responses may remain effective and prevent severe disease in most cases [ 108 , 109 ]. Altogether, SARS-CoV-2 continues to infect humans but in relatively stable numbers, and has transitioned from the pandemic to the endemic phase [ 110 , 111 ].…”

Section: Evasion Of Adaptive Immunitymentioning

confidence: 99%

Causes and Consequences of Coronavirus Spike Protein Variability

Zech,

Jung,

Jacob

et al. 2024

Viruses

View full text Add to dashboard Cite

Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines.

show abstract

The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection

Cited by 36 publications

References 112 publications

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19

Causes and Consequences of Coronavirus Spike Protein Variability

Contact Info

Product

Resources

About