An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection

Ley, P.A. van der; Zariri, Afshin; Riet, Elly van; Oosterhoff, Dinja; Kruiswijk, Corine P.

doi:10.3389/fimmu.2021.781280

Cited by 82 publications

(52 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional studies will need to be performed to verify the opsonizing activity of anti-GAC-GMMA antibodies and compare GAC-GMMA with other vaccines in development against GAS by use of a challenge model. Furthermore, recent publications have shown that OMV are able to promote a mucosal immune response [ 61 , 62 ]. We also aim to verify this for GAC-GMMA, performing additional studies to verify the ability of GAC-GMMA to elicit mucosal immunity, always in comparison to GAC-CRM 197 .…”

Section: Discussionmentioning

confidence: 99%

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

et al. 2022

View full text Add to dashboard Cite

Group A Streptococcus (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM197; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM197 in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM197, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM197. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden.

show abstract

Section: Discussionmentioning

confidence: 99%

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Antiviral prophylactics can provide vital assistance to vaccines by providing an orthogonal selection pressure (on non-spike proteins) that retards the emergence of novel immune-evasive variants. Multiple groups have reported the robust induction of mucosal immunity with nasal SARS-CoV-2 vaccines 97–105 , and designing such vaccines to be robust to viral evolution would provide a powerful tool for limiting transmission. It is imperative to improve our range of biomedical interventions that can reduce viral transmission and to formulate a public-health strategy that also relies on passive nonpharmaceutical interventions (such as improved ventilation and air quality).…”

Section: Discussionmentioning

confidence: 99%

Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

Stoddard¹,

Novokhodko

Sarkar

et al. 2022

Preprint

View full text Add to dashboard Cite

We have entered a new phase of the ongoing COVID-19 pandemic, as the strategy of relying solely on the current SARS-CoV-2 vaccines to bring the pandemic to an end has become infeasible. In response, public-health authorities in many countries have advocated for a strategy of using the vaccines to limit morbidity and mortality while permitting unchecked SARS-CoV-2 spread ("learning to live with the disease"). The feasibility of this strategy is critically dependent on the infection fatality rate (IFR) of COVID-19. An expectation exists, both in the lay public and in the scientific community, that future waves of the virus will exhibit decreased IFR, either due to viral attenuation or the progressive buildup of immunity. In this work, we examine the basis for that expectation, assessing the impact of virulence on transmission. Our findings suggest that large increases in virulence for SARS-CoV-2 would result in minimal loss of transmission, implying that the IFR may be free to increase or decrease under neutral evolutionary drift. We further examine the effect of changes in the IFR on the steady-state death toll under conditions of endemic COVID-19. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to an unsustainable mortality burden. Our findings thus highlight the critical importance of enacting a concerted strategy (involving for example global access to vaccines, therapeutics, prophylactics and nonpharmaceutical interventions) to suppress SARS-CoV-2 transmission, thereby reducing the risk of catastrophic outcomes. Our findings also highlight the importance of continued investment in novel biomedical interventions to prevent viral transmission.

show abstract

“…This may contribute to how human milk protects against mucosal infections in the human milk-fed infant. Nine intranasal vaccines are currently in clinical development to prevent infection and transmission of SARS-CoV-2 with promising data in animal models [52][53][54] . LAIV is one of the few mucosally delivered vaccines; our findings likely apply to other mucosal vaccines and infections.…”

Section: Discussionmentioning

confidence: 99%

Molecular alterations in human milk in simulated maternal nasal mucosal infection with live attenuated influenza vaccination

et al. 2022

View full text Add to dashboard Cite

Breastfeeding protects against mucosal infections in infants. The underlying mechanisms through which immunity develops in human milk following maternal infection with mucosal pathogens are not well understood. We simulated nasal mucosal influenza infection through live attenuated influenza vaccination (LAIV) and compared immune responses in milk to inactivated influenza vaccination (IIV). Transcriptomic analysis was performed on RNA extracted from human milk cells to evaluate differentially expressed genes and pathways on days 1 and 7 post-vaccination. Both LAIV and IIV vaccines induced influenza-specific IgA that persisted for at least 6 months. Regulation of type I interferon production, toll-like receptor, and pattern recognition receptor signaling pathways were highly upregulated in milk on day 1 following LAIV but not IIV at any time point. Upregulation of innate immunity in human milk may provide timely protection against mucosal infections until antigen-specific immunity develops in the human milk-fed infant.

show abstract

An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection

Cited by 82 publications

References 56 publications

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

Molecular alterations in human milk in simulated maternal nasal mucosal infection with live attenuated influenza vaccination

Contact Info

Product

Resources

About