Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective

Zhang, Yuexiu; Chamblee, Michelle; Xu, Jiayu; Qu, Panke; Shamseldin, Mohamed M.; Yoo, Sung J.; Misny, Jack; Thongpan, Ilada; KC, Mahesh; Hall, Jesse M.; Gupta, Yash A.; Evans, John P.; Lu, Mijia; Ye, Chengjin; Hsu, Cheng Chih; Liang, Xueya; Martinez-Sobrido, Luis; Yount, Jacob S.; Boyaka, Prosper N.; Liu, Shan-Lu; Dubey, Purnima; Peeples, Mark E.; Li, Jianrong

doi:10.1038/s41467-024-49443-2

Cited by 3 publications

References 60 publications

(76 reference statements)

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Induction of tissue resident memory T cells by measles vaccine vector

Vera-Peralta,

Ruffié,

Najburg

et al. 2024

Human Vaccines & Immunotherapeutics

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Measles live attenuated vaccine (MV) induces strong humoral and cellular systemic memory responses allowing the successful control of measles since decades. MV has also been adapted into a promising vaccine platform with several vaccine candidates in clinical development. To understand and document the tissue-scaled memory response induced by MV, we explored the specific induction and persistence of resident memory T cells (Trm) in the lungs and the liver, two critical targeted tissues for vaccine development against several diseases. Trm are a subset of non-circulating highly specialized T cells. They are found at multiple barrier and mucosal sites, conveniently positioned to rapidly react against pathogens. The induction of Trm in different tissues is therefore critical for vaccine development. We demonstrated in mice the rapid generation of MV-specific and vectorized antigen-specific Trm in the liver and the lungs after a single dose, whatever the route of immunization. The intranasal route induced more Trm in the lungs than other routes, confirming the potential of intranasal vaccine administration of replicative viral vectors to generate a strong pulmonary immune response. MV-specific Trm cells were functionally active, with CD8 + Trm secreting granzyme B upon in vitro restimulation and CD4 + Trm cells secreting IFN-γ and TNF-α. We confirmed in human lymphocytes this tissue tropism by showing an overexpression of homing receptors directing them to epithelial and inflamed tissues. Vaccination strategies able to induce Trm cells at key sites represent a promising field to improve current vaccines, prioritize vaccine platforms and design future vaccines with enhanced protective efficacy.

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Induction of tissue resident memory T cells by measles vaccine vector

Vera-Peralta,

Ruffié,

Najburg

et al. 2024

Human Vaccines & Immunotherapeutics

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Immunologic and Biophysical Features of the BNT162b2 JN.1- and KP.2-Adapted COVID-19 Vaccines

Chen,

Tompkins,

Windsor

et al. 2024

Preprint

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Vaccines remain a vital public health tool to reduce the burden of COVID-19. COVID-19 vaccines that are more closely matched to circulating SARS-CoV-2 lineages elicit more potent and relevant immune responses that translate to improved real-world vaccine effectiveness. The rise in prevalence of the Omicron JN.1 lineage, and subsequent derivative sublineages such as KP.2 and KP.3, coincided with reduced neutralizing activity and effectiveness of Omicron XBB.1.5-adapted vaccines. Here, we characterized the biophysical and immunologic attributes of BNT162b2 JN.1- and KP.2-adapted mRNA vaccine-encoded spike (S) protein immunogens. Biophysical interrogations of S revealed the structural consequences of hallmark amino acid substitutions and a potential molecular mechanism of immune escape employed by JN.1 and KP.2. The vaccine candidates were evaluated for their immunogenicity when administered as fourth or fifth doses in BNT162b2-experienced mice or as a primary series in naïve mice. In both vaccine-experienced and naïve settings, JN.1- and KP.2-adapted vaccines conferred improved neutralizing responses over the BNT162b2 XBB.1.5 vaccine against a broad panel of emerging JN.1 sublineages, including the predominant KP.3.1.1 and emerging XEC lineages. Antigenic mapping of neutralizing responses indicated greater antigenic overlap of JN.1- and KP.2-adapted vaccine responses with currently circulating sublineages compared to an XBB.1.5-adapted vaccine. CD4+ and CD8+ T cell responses were generally conserved across all three vaccines. Together, the data support the selection of JN.1- or KP.2-adapted vaccines for the 2024-25 COVID-19 vaccine formula.

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mRNA Vaccines Against COVID-19 as Trailblazers for Other Human Infectious Diseases

Brandi,

Paganelli,

D’Amelio

et al. 2024

Vaccines

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mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases. Results: RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed. Conclusions: The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet.

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Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective

Cited by 3 publications

References 60 publications

Induction of tissue resident memory T cells by measles vaccine vector

Induction of tissue resident memory T cells by measles vaccine vector

Immunologic and Biophysical Features of the BNT162b2 JN.1- and KP.2-Adapted COVID-19 Vaccines

mRNA Vaccines Against COVID-19 as Trailblazers for Other Human Infectious Diseases

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