• Product Name: rBCG-N-hRSV
• Manufacturer: IDT Biologika
• Type: Recombinant vector vaccine
• Status: Clinical trial
• Location Licensed: Pontifcia Universidad Catholics de Chile
• Host Species for Licensed Use: None
• Antigen: (Abarca et al., 2020) N protein
• Vector: (Abarca et al., 2020) Bacillus Calmette-Guerin-Gudrun (BCG) is used as a vector.
• Preservative: (Abarca et al., 2020) Antigen T cells
• Preparation: 0.05 mL of a reconstituted vial (2-8*10^6 CFU of the bacteria per 0.1 mL) of this vaccine is administered. This results in 1-4*10^5 CFU to a newborn.
• Immunization Route: Intradermal injection (i.d.)
• Description: (Abarca et al., 2020) rBCG-N-hRSV is a live attenuated recombinant Mycobacterium bovis BCG based on the Danish strain 1331 that expresses the nucleoprotein (N) of RSV (rBCG-N-hRSV)(BCG) that expresses the nuclei protein (N) of RSV.

• Tradename: Fluarix
• Manufacturer: Janssen (Leiden, the Netherlands)
• Type: Other
• Status: Licensed
• Host Species for Licensed Use: Human
• Antigen: 4 virus strains (15 μg of hemagglutinin per strain per 0.5-mL dose): A/Singapore/GP1908/2015 (H1N1) IVR-180, A/Hong Kong/4801/2014 (H3N2) NYMC X-263B, B/Phuket/3073/2013, and B/Brisbane/60/2008. The placebo was sterile 0.9% saline.
• Vector: (Sadoff et al., 2021)An adenovirus serotype 26 (Ad26) vector
• Preparation: (Sadoff et al., 2021) Each 0.5-mL dose contained 1 × 1011 viral particles (vp) of Ad26.RSV.preF. Fluarix Quadrivalent (GlaxoSmithKline), formulated for the 2017–2018 Northern Hemisphere season, contained the following 4 virus strains (15 μg of hemagglutinin per strain per 0.5-mL dose): A/Singapore/GP1908/2015 (H1N1) IVR-180, A/Hong Kong/4801/2014 (H3N2) NYMC X-263B, B/Phuket/3073/2013, and B/Brisbane/60/2008. The placebo was sterile 0.9% saline.
• Immunization Route: Intramuscular injection (i.m.)
• Description: (Sadoff et al., 2021) The vaccine Ad26.RSV.preF is the next-generation vaccine expressing the stabilized FA2. The vaccine is a replication-incompetent Ad26 vector containing a DNA transgene, encoding a F protein derived from the RSV A2 strain that is stabilized in its pre-F conformation

• Manufacturer: Charles river Laboratories
• Type: Live, attenuated vaccine
• Status: Licensed
• Host Species for Licensed Use: Human
• M2-2 gene engineering:
  • Type: Deletion
  • Description: (McFarland et al., 2020)The vaccine uses backbone of LId/M2-2 vaccine but has a 234 nucleotide M2-2 deletion with the same structure as in MEDI/m2-2
  • Detailed Gene Information: Click Here.
• Immunization Route: intranasal immunization
• Description: (McFarland et al., 2020)The vaccine, D46/NS2/N/ΔM2-2-HindIII, is a cDNA-derived version of RSV subgroup A, strain A2. In addition, D46/NS2/N/ΔM2-2-HindIII has the MEDI/ΔM2-2 assignments at the only 2 amino acid positions that differ between MEDI/ΔM2-2 and LID/ΔM2-2. D46/NS2/N/ΔM2-2-HindIII contains the complete 112-nucleotide 3’ noncoding region of the SH gene that is present in biological RSV A2 but was deleted in LID/ΔM2-2. D46/NS2/N/ΔM2-2-HindIII was recovered from cDNA in qualified Vero cells.

• Manufacturer: Charles River Laboratories Malvern, PA
• Type: Live, attenuated vaccine
• Status: Clinical trial
• Host Species for Licensed Use: None
• M2-2 gene engineering:
  • Type: Recombinant protein preparation
  • Description: 241 deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 (McFarland et al., 2020).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intramuscular injection (i.m.)
• Description: The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2 with 241 nts deleted from the M2-2 ORF and the 3 potential translation initiation codons of the M2-2 ORF silenced (McFarland et al., 2020).

• Type: Subunit vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Antigen: F protein
• F protein gene engineering:
  • Type: Recombinant protein preparation
  • Description: A trimeric F glycoproteins from both major RSV subgroups (A and B) engineered for stability in the prefusion conformation is in clinical development in adults (Falsey et al., 2022).
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0000127
  • Description: (Falsey et al., 2022)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A bivalent prefusion F vaccine (RSVpreF) containing trimeric F glycoproteins from both major RSV subgroups (A and B) engineered for stability in the prefusion conformation is in clinical development in adult (Falsey et al., 2022).

• Manufacturer: Charles River Laboratories
• Type: Live, attenuated vaccine
• Status: Research
• Host Species for Licensed Use: Human
• F protein gene engineering:
  • Type: Gene mutation
  • Description: (Karron et al., 2020)Has a 523 nucleotide deletion of the NS2 gene. RSV/ΔNS2/Δ1313/I1314L was derived from a recombinant version of wt RSV strain A2 with the further modification of a 112 nucleotide phenotypically silent deletion in the SH noncoding sequence that stabilizes the complementary DNA (cDNA) during propagation in bacteria.
  • Detailed Gene Information: Click Here.
• F protein gene engineering:
  • Type: Codon deletion
  • Description: (Karron et al., 2020)A codon deletion in the L gene (Δ1313; deletion of S1313) plus the adjacent missense mutation I1314L that prevents the compensatory deattenuating mutation I1314T. RSV/ΔNS2/Δ1313/I1314L was derived from a recombinant version of wt RSV strain A2 with the further modification of a 112 nucleotide phenotypically silent deletion in the SH noncoding sequence that stabilizes the complementary DNA (cDNA) during propagation in bacteria.
  • Detailed Gene Information: Click Here.
• Immunization Route: Intramuscular injection (i.m.)
• Storage: (Karron et al., 2020)CTM was stored at −70°C and diluted to dose on site using Leibovitz L15 medium.
• Description: (Karron et al., 2020)RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L.

Human Response

• Host Strain: Danish strain
• Vaccination Protocol: In each cohort, participants were vaccinated with 0.1 mL of the vaccine, as follows: 6 volunteers in Cohort A were vaccinated with the lowest dose (5 × 10^3 CFU); 6 volunteers in Cohort B received the middle dose (5 × 10^4 CFU); 6 volunteers in Cohort C received the highest dose (1 × 10^5 CFU) of the study vaccine. Each cohort included two volunteers vaccinated with 0.1 mL of the standard BCG vaccine (BCG-WT; a full dose of 1-33 × 10^5 CFU).
• Vaccination Groups:

  No.	Group Name	Number of Animals	Dose	Route	Gender	Age	Control Group?	Comment	Vaccination Detail
  1	BCG control vaccine		1-33*10^5 CFU in volume 0.1 ml	Intradermal injection (i.d.)	male	18-50 year	yes	Each cohort included 2 volunteers with the standard BCG vaccine as the control group
  2	Cohort A		5*10^3 CFU in volume 0.1 ml	Intradermal injection (i.d.)	male	18-50 year	no
  3	Cohort B		5*10^4 CFU in volume 0.1 ml	Intradermal injection (i.d.)	male	18-50 year	no
  4	Cohort C		1*10^5 CFU in volume 0.1 ml	Intradermal injection (i.d.)	male	18-50 year	no

• Immune Response: (Abarca et al., 2020) Both immunogenicity and reactogenicity responses were lower in BCG-WT immunized volunteers as compared to volunteers immunized with the study vaccine. N-RSV immune responses increased with higher doses of the vaccine
• Side Effects: (Abarca et al., 2020) General (systemic) solicited AEs included fever, tachycardia, hypo/hypertension, headache, fatigue, myalgia, nausea/vomiting, and diarrhea.
• Challenge Protocol: The findings with rBCG-N-hRSV vaccine are consistent with previous studies that showed that it induces a Th-1 RSV-specific immune response in mice, which was protective against RSV challenge
• Efficacy: (Abarca et al., 2020) rBCG-N-hRSV vaccine candidate was safe, well tolerated, and immunogenicity in healthy male adult volunteers. Both immunogenicity and reactogenicity responses were lower in control group as compared to volunteers immunized with the study vaccine. Individuals did not show enhancement of RSV disease.

Human Response

• Vaccination Protocol: In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control).
• Challenge Protocol: (Sadoff et al., 2021) Adenoviral vectors adenovirus serotypes 26 and 35 (Ad26 and Ad35), expressing the nonstabilized form of the F protein of the RSV strain A2 induced strong RSV specific humoral and cellular immune responses in mice and were protective in the cotton rat challenge model. Ad26 vectors encoding the RSV F glycoprotein, the most immunogenic antigen in a RSV vaccine [24, 26, 28], have demonstrated high and durable RSV neutralizing antibody titers, a T-helper 1–type cellular immune response and protective immunity in an animal challenge model
• Efficacy: Reported systemic reactogenicity and those graded 3 were generally more frequent after dosing with Ad26.RSV.preF than with Fluarix alone. Systemic reactogenicity was also higher after vaccination with Ad26.RSV.preF alone and in combination with Fluarix in this study than after vaccination with Ad26.RSV.preF alone, as previously reported in study VAC18193RSV1003 for a similar age group. Ad26.RSVpreF was generally well tolerated and had an acceptable safety profile(Sadoff et al., 2021)

Human Response

• Vaccination Protocol: he study included children ≥6 and <25 months of age who were healthy, had no current or past lung disease, and were RSV seronegative at screening (McFarland et al., 2020)
• Side Effects: During the 28 days after inoculation, mild upper respiratory tract and/or febrile events occurred in both vaccine and placebo recipients, with 76%. All respiratory symptoms in both groups were grade 1. Grade 2 fever occurred in 1 vaccinee and 1 placebo recipient. Of the 16 vaccinees with respiratory or febrile illness, illness was concurrent with vaccine alone detected in NW specimens in 12, vaccine plus rhinovirus in 2, vaccine plus rhinovirus and adenovirus in 1, and parainfluenza type 4 and no vaccine virus in 1. (McFarland et al., 2020)
• Efficacy: (McFarland et al., 2020) When administered to RSV-naive 6–24 month-old infants and children, the RSV D46/NS2/N/ΔM2-2-HindIII candidate vaccine was well tolerated, was highly infectious (100% of participants had evidence of vaccine shedding and/or a serum RSV antibody response), and resulted in excellent induction of serum RSV-specific antibodies, including neutralizing antibodies.
• Description: (McFarland et al., 2020)The D46/NS2/N/ΔM2-2-HindIII vaccine had excellent infectivity and generated robust neutralizing antibody and anti-RSV F protein IgG responses.

Human Response

• Vaccination Protocol: (McFarland et al., 2020)Eligible children were RSV seronegative at screening, defined as having a complement-enhanced serum RSV 60% plaque reduction neutralizing titer. Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.
• Challenge Protocol: (McFarland et al., 2020)The small sample size precludes firm estimates of rates of vaccine-associated events, infectivity, immunogenicity, and viral replication.
• Efficacy: (McFarland et al., 2020)Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.
• Description: The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2. The results showed that the LID/∆M2-2/1030s is a very attractive candidate for further development as a live attenuated in trans Al pediatric RSV vaccine.

Human Response

• Vaccination Protocol: Patient was given a single 60-µg, 120-µg or 240-µg dose on day 0.
• Immune Response: Among older adults 65–85 years in the expanded cohort, RSV A 50% neutralizing GMTs in RSVpreF recipients increased from 1793–2734 before vaccination to 14 905–27 600 at 1 month postvaccination (Figure 3). RSV B neutralizing titers increased from 1635–2685 before vaccination to 15 169–30 071 at 1 month postvaccination. Postimmunization neutralizing titers were similarly high across RSVpreF dose levels and formulations; corresponding GMFRs were 7.2–13.2 for RSV A and 6.9–14.9 for RSV B across RSVpreF groups, and 1.1 for RSV A and 0.9 for RSV B for placebo recipients (findings were similar for older adults in the sentinel cohort.
• Side Effects: 124/490 of participants in the RSVpreF cohorts had local reactions within 14 days post–vaccination. The majority (82.2% [102/124]) of participants who reported local reactions rated them mild in severity; pain at the injection site was the most common (22.2% [109/490]) (Falsey et al., 2022).

Human Response

• Vaccination Protocol: (Karron et al., 2020) Children were given a dose of 10^6 PFU and in RSV-seronegative children at a dose of 10^5 or 10^6 PFU (Figure 1). Children were randomized 2:1 to receive vaccine or placebo, administered as nose drops
• Side Effects: (Karron et al., 2020)In RSV-seropositive participants, URI was observed in 2 and cough was observed in 1 of 10 vaccinees during the 28-day postimmunization reporting period (Table 1); in each case, rhinovirus was detected in NW samples at the time of illness. None of the vaccinees shed vaccine virus, indicative of attenuation.
• Efficacy: The vaccination showed statistically significant differences in log-fold plaque reduction neutralization antibody titers and the presence of 4-fold increase in RSV F IgG response in both seropositive and seronegative responses. However, 16/20 seropositive and 17/20 seronegative children in the placebo group did have RSV neutralizing antibody responses occured in 16 of 20 and F IgG responses in 17 of 20 RSV-seronegative children who received 106 PFU . For recipients of 105 and  106 PFU, the mean postvaccination PRNT was  1:37 and 1:64, respectively. (Karron et al., 2020)