In macaques, a mucosal COVID vaccination candidate is highly protective.

In macaques, a mucosal COVID vaccination candidate is highly protective.

In macaques, a recent study published on the bioRxiv* preprint server showed that the intranasal paediatric parainfluenza virus-vectored coronavirus disease 2019 (COVID-19) vaccine candidate, B/HPIV3/S-6P, had protective effectiveness.

Background

SARS-CoV-2 is a severe acute respiratory syndrome coronavirus that can infect persons of any age. Thousands of children have been taken to hospitals in the United States (US) as a result of SARS-CoV-2 infection, with about one-third of them having no prior medical difficulties. Over 800 US children aged 0 to 11 years have died as a result of COVID-19, and children accounted for more than 25% of COVID-19 cases during the US SARS-CoV-2 outbreak in the fall/winter of 2021/2022. Furthermore, in children, COVID-19 seldom causes a multisystem inflammatory illness (MIS-C).

Vaccines against SARS-CoV-2 messenger ribonucleic acid (mRNA) are available for children aged five and up, but none has been licenced or recommended for children under the age of five. Furthermore, the existing SARS-CoV-2 mRNA and other parenteral vaccines have a limitation in that they do not produce direct protection in the respiratory tract, which is where SARS-CoV-2 multiplication, entry, egress, and sickness occur. As a result, paediatric COVID-19 vaccinations must provide both systemic and mucosal immunity.

Concerning the research

The researchers created B/HPIV3/S-6P, a live-attenuated chimeric bovine/human parainfluenza virus type-3 (B/HPIV3)-vectored COVID-19 vaccine option with prefusion-stabilized SARS-CoV-2 spike (S) protein, in the current study. The B/HPIV3 vector was originally created as a paediatric vaccine candidate for HPIV3, a negative-sense single-stranded RNA virus that is a prominent cause of respiratory disease, particularly in newborns and young children under the age of five.

The authors of this study recently demonstrated that B/HPIV3 containing perfusion-stabilized SARS-CoV-2 S protein effectively protected hamsters from a vaccine antigen-matched SARS-CoV-2 isolate infection, reducing SARS-CoV-2 replication in the lower and upper respiratory tract and preventing lung inflammation and weight loss.

The immunogenicity, safety, and protective capacity of a single dose of intratracheal/intranasal (IT/IN) B/HPIV3/S-6P immunisation in rhesus macaques were investigated in this work (RMs). To investigate immunogenicity, they measured SARS-CoV-2 S-specific T-cell, systemic, and mucosal antibody responses. They also looked at neutralising antibody responses of B/HPIV3/S-6P in vaccinated RMs to the vaccine-matched SARS-CoV-2 strand as well as the SARS-CoV-2 Omicron BA.1, Delta, Beta, and Alpha variants of concern (VOCs). Furthermore, before moving on with a Phase I clinical study, the scientists tested B/HPIV3/capacity S-6P's to defend against the SARS-CoV-2 challenge.

Conclusions and findings

According to the findings, B/HPIV3/S-6P and B/HPIV3 had no effect on the overall health of RMs after vaccination, indicating that the expressed SARS-CoV-2 S protein and vector were safe in this non-human primate species. SARS-CoV-2 S-specific mucosal immunoglobulin G (IgG) and IgA responses were elicited in the airway after a single intratracheal/intranasal B/HPIV3/S-6P vaccination dose. High serum SARS-CoV-2 receptor-binding domain (RBD) and S-specific antibody titers (IgA, IgM, and IgG) were also obtained after vaccination, successfully neutralising the SARS-CoV-2 VOCs. Anti-RBD and anti-S IgG responses were comparable to those observed in human convalescent plasma with high anti-RBD and anti-S IgG antibody titers.

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Mucosal antibody responses to SARS-CoV-2 S are induced in the upper and lower airways after intranasal/intratracheal immunisation with B/HPIV3/S-6P. The intranasal/intratracheal method was used to immunise rhesus macaques (n=4) with B/HPIV3/S-6P or B/HPIV3 (control) (Figure S1). Nasal washes (NW) were done before immunisation and on days 14, 21, and 28 to measure the mucosal antibody response in the upper airways. Bronchoalveolar lavages (BAL) were taken before immunisation and on days 9, 21, and 28 pi to assess the antibody response in the lower airways. (A and B) S- and RBD-specific mucosal IgA and IgG titers in the upper (A) and lower (B) airways on specified days post-immunization (pi), as assessed by time. -dissociation that has been resolved -Immunoassay for lanthanide fluorescence (DELFIA-TRF). For the endpoint titers, log10 is used.

mucosal IgA and IgG to a secreted prefusion-stabilized form of the S protein (aa 1-1,208; S-2P) (left panels) or to a fragment of the S protein (aa 328-531) containing SARS-CoV-2 RBD (right panels) (right panels). The detection limit is 1.6 log10 (dotted line). B/HPIV3/S-6P-immunized RMs are depicted in blue, while B/HPIV3-immunized RMs are depicted in green, with each RM denoted by a symbol (two-way ANOVA, Sidak multiple comparison test).

Serum antibodies effectively neutralised the vaccine-matched SARS-CoV-2 WA1/2020 isolate as well as the Alpha and Delta VOCs. Despite this, these sera had only a minor neutralising effect on the Beta and Omicron VOCs. This implied that a booster dose of B/HPIV3/S-6P, comparable to any SARS-CoV-2 vaccine, might be required to improve antibody concentrations and affinity maturation, allowing for a wider spectrum of antigen identification and VOC protection.

Although this has not been proven, B/HPIV3/S-6P vaccination likely resulted in long-lived antigen-selective tissue-resident T and B cells in the mucosa. B/HPIV3/S-6P induced robust S-specific CD8+ and CD4+ T-cell responses in the lungs and throughout the body, primarily in lung tissue-resident memory cells.

After the viral challenge, SARS-CoV-2 replication in vaccinated macaques' lung tissues and airways was undetectable. One month after immunisation, RMs were totally protected against the SARS-CoV-2 challenge. No SARS-CoV-2 challenge virus multiplication was identified in the airways or lung tissues of vaccinated RMs under the current experimental conditions, implying sterilising immunity. The durability of protection, on the other hand, was unknown and will be studied in a future study. The authors discovered a recall reflex of S-specific CD4+ T-cells from B/HPIV3/S-6P-vaccinated RMs in the blood after the challenge, but not in the lower airway.

In conclusion, a single topical B/HPIV3/S-6P vaccination was found to be strongly protective and immunogenic against COVID-19 in rhesus macaques. The current data suggest that this vaccine could be developed as a standalone vaccine or in a prime/boost combination with existing SARS-CoV-2 vaccinations for infants and young children. According to the authors, a phase I trial will be conducted on B/HPIV3/S-6P.

*Notice: bioRxiv publishes preliminary scientific studies that have not been peer-reviewed and should not be regarded as conclusive, should not be used to influence clinical treatment or health-related behaviour, and should not be seen as established information.