A recent research paper was published to bioRxiv* Prepress server demonstrates the preventive efficacy of the pediatric influenza virus disease 2019 (COVID-19) virus, B/HPIV3/S-6P, in macaques.
Study: The pediatric intranasal SARS-CoV-2 influenza virus vaccine is prophylactic in macaques. Image Credit: NIAID
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect people of any age. Although COVID-19 is often mild in young children compared to adults, thousands of children have been hospitalized in the United States (US) due to SARS-CoV-2 infection, with one third of them having no previous medical problems. More than 800 American children ages 0-11 have died from COVID-19, and during the fall-winter 2021/2022 SARS outbreak in the United States, children made up more than 25% of COVID-19 cases. Furthermore, COVID-19 rarely results in a pediatric multisystem inflammatory disease (MIS-C).
While SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccines are available for children aged five years or older, a vaccine for children under five has not been approved or recommended. Furthermore, the drawback of current SARS-CoV-2 mRNA and other parenteral vaccines is that they did not directly stimulate immunity in the respiratory tract, where SARS-CoV-2 replication, entry, exit, and disease primarily occur. Therefore, COVID-19 vaccines for children that transmit systemic and mucosal immunity are required.
In the current work, scientists have developed B/HPIV3/S-6P, a live attenuated variant of human bovine chimeric virus/human parainfluenza type 3 (B/HPIV3)—a mutant COVID-19 vaccine that contains stable SARS-CoV-2. Advance Spike Protein (S). Interestingly, the B/HPIV3 vector was initially developed as a possibility to inoculate children with the negative sense single-stranded RNA virus, HPIV3, which is a major cause of respiratory illness, particularly in infants and young children under 5 years of age.
The authors of the current research recently demonstrated that the perfusion-stabilized SARS-CoV-2 S protein B/HPIV3 effectively protects hamsters from vaccine antigen-matched SARS-CoV-2 isolate infection, deters lung inflammation, reduces weight, and efficiently lowers SARS-CoV replication. CoV-2 in the lower and upper respiratory tract.
In this study, the team tested the immunogenicity, safety, and protection of a single dose of intratracheal/intranasal (IT/IN) B/HIPIV3/S-6P vaccination in macaques (RMs). They identified T-cell, systemic, and mucosal responses specific to SARS-CoV-2 S to assess immunogenicity. In addition, they analyzed the responses of B/HPIV3/S-6P neutralizing antibodies to the vaccine-matched SARS-CoV-2 strand and the SARS-CoV-2 Omicron BA.1, Delta, Beta, and Alpha variants of concern (Volatile Organic Compounds) ) in inoculated RMs. Besides, prior to advancing B/HPIV3/S-6P to phase I clinical trial, the team evaluated the protective ability of B/HPIV3/S-6P against the SARS-CoV-2 challenge.
RESULTS AND CONCLUSIONS
According to the results of the study, after vaccination, B/HPIV3/S-6P and B/HPIV3 did not affect the overall health of RMs, showing that the expressed SARS-CoV-2 S protein and this vector was safe in this non-human. Primate types. A single dose of intratracheal/intranasal B/HPIV3/S-6P vaccine generated robust responses of mucosal immunoglobulin G (IgG) and IgA in the airway. Vaccination also caused an elevation of the SARS-CoV-2 receptor binding domain (RBD) and S-specific antibodies (IgA, IgM and IgG), effectively neutralizing SARS-CoV-2 VOCs. Anti-RBD and anti-S IgG responses were equivalent to those in human convalescent plasma with high titers of anti-RBD and anti-S IgG antibodies.
Intranasal/endobronchial immunization with B/HPIV3/S-6P induces mucosal antibody responses to SARS-CoV-2 S in the upper and lower airways. Rhesus macaques (n = 4 per group) were vaccinated with B/HPIV3/S-6P or B/HPIV3 (control) nasally/intratracheally (Fig. S1). To determine the mucosal antibody response in the upper airways, nasal lavage (NW) was performed before vaccination and on days 14, 21 and 28. To analyze the antibody response in the lower airways, bronchoalveolar lavage (BAL) was collected before vaccination and on days 9, 21 and 28 pi. (a And the B) S- and receptor-binding domain (RBD)-specific mucosal IgA and IgG titers on specific days after immunization (pi) in the upper (A) and lower (B) airways, which are determined by time-resolved dissociation, enhance Lanthanide fluorescence (DELFIA-TRF) immunostaining. Endpoint counters are expressed in the log10 For mucosal IgA and IgG to a stable secreted, pre-infusion (aa 1-1,208; S-2P) form of S protein (left panels) or a fragment of S protein (aa 328-531) containing SARS-CoV-2 RBD (right panels). The detection limit is 1.6 records10 (dotted line). B/HPIV3/S-6P-immunized RMs are shown in blue, while B/HIPIV3-immunized RMs are in green, with each RM represented by a symbol. *P < 0.05 (two-way ANOVA, Sidak's multiple comparison test).
The SARS-CoV-2 WA1 / 2020 isolate identical to the vaccine and alpha and delta VOCs were efficiently neutralized by antibodies in the blood. However, these serums had negligible neutralizing efficacy against beta VOCs and omicron. This finding demonstrated that a booster dose of B/HPIV3/S-6P similar to any vaccine against SARS-CoV-2 may be necessary to increase antibody concentrations and affinity maturation, allowing a broader range of antigen identification and immunity to VOCs.
B/HPIV3/S-6P vaccination likely produces long-lived antigen-selective tissue-resident T and B cells in the mucosa, although this has not been confirmed. B/HPIV3/S-6P elicited robust and systemic pulmonary responses specific to S CD8 and CD4+ T, consisting of lung tissue-resident memory cells.
Replication of SARS-CoV-2 in lung tissue and airways of immunized macaques was undetectable after viral challenge. RMs were completely protected from SARS-CoV-2 challenge one month after vaccination. Under the current experimental conditions, replication of SARS-CoV-2 challenge viruses was not detected in the airways, or lung tissues of vaccinated RMs, implying sterile immunity. On the other hand, the durability of the protection is still unknown and will be investigated in a later study. After the challenge, the authors found a reversal of CD4+ T-cell retrieval of S-specific B/HPIV3/S-6P-immunized B/HIV3/S-6P cells in the blood but not in the lower airway.
In summary, the study results showed that a single topical B/HPIV3/S-6P vaccine was significantly protective and immunosuppressive against COVID-19 in rhesus macaques. The current data encourage development of the potential for this vaccine as a single vaccine or in a prime/booster combination with existing SARS-CoV-2 vaccines for newborns and young children. According to the authors, a phase 1 trial will also be conducted on B/HPIV3/S-6P.
bioRxiv publishes preliminary scientific reports that are not subject to peer review, and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.
- The SARS-CoV-2 intranasal influenza virus vector vaccine in children is prophylactic in macaques; Cyril Lee Noen, Kristen E. Nelson, Chioqiao Liu, Hong-Su Park, Yumiko Matsuoka, Cindy Longo, Celia Santos, Lijuan Yang, Richard Herbert, Ashley Castins, Ian In Moore, Timeri Wilder-Coffee, Rashida Moore, April Walker, Bing Chang, Paulo Luso, Red F Johnson, Nicole El Garza, Laura E. Villa, Sherine Mounir, Daniel Barber, Ursula J. Buchholz. Prepare bioRxiv 2022. DOI: https://doi.org/10.1101/2022.05.21.492923, https://www.biorxiv.org/content/10.1101/2022.05.21.4922923v1