An article published in the journal Science Translational Medicine in February presented encouraging results from the phase 1 clinical trials of HXP-GPOVac, Thailand’s COVID-19 vaccine candidate developed from the NDV-HXP-S technology platform, originally created at Mount Sinai Hospital in the USA. The vaccine was tested on 210 people in Thailand and produced a similar immune response against SARS-CoV-2 as provided by the messenger RNA (mRNA) vaccine manufactured by American pharmaceutical company Pfizer in partnership with German company BioNTech.
The profiles of the antibodies produced by the two vaccines, however, were different. HXP-GPOVac generated more neutralizing antibodies than the Pfizer/BioNTech vaccine, but fewer non-neutralizing (binding) antibodies. The former prevent viruses from invading cells and multiplying inside them, while the latter, known as ligands, mark the virus and alert the immune system to destroy any cells occupied by the infectious agent. “This means that the immune response stimulated by HXP-GPOVac is more focused on neutralization,” explained microbiologist Florian Krammer of the Icahn School of Medicine at Mount Sinai, coordinator of the study, in an interview with Pesquisa FAPESP.
Vaccines that produce large amounts of neutralizing antibodies are considered sterilizing because they have the potential to block infection and prevent development of disease. Those that produce a mixture of the two types of antibodies do not prevent infection, but protect against severe forms of the disease. In the case of COVID-19, the neutralizing effect is conferred by antibodies that adhere to a very specific region of the spike protein that the virus uses to invade cells called the receptor-binding domain (RDB), the virus’s Achilles heel.
The data presented in the study is good news not only for Thailand. The formulation evaluated in the country, manufactured by Thailand’s Government Pharmaceutical Organization (GPO), is almost identical to the vaccine candidates being developed and tested in Vietnam and Brazil. Brazil’s version, named ButanVac, was developed by the Butantan Institute in São Paulo, in partnership with the same international consortium as the Americans, Thais, and Vietnamese. Vietnam’s vaccine is called CoviVac.
ButanVac, CoviVac, and HXP-GPOVac are all based on the same foundation. The three formulations use an inactivated version of the Newcastle disease virus—which causes a respiratory infection in birds, but is harmless to humans—that has been genetically engineered to produce a more stable form of the coronavirus’s spike protein. A team led by Mount Sinai virologist Peter Palese developed the vaccine platform with the hope that it would be used to make a low-cost vaccine that could be manufactured by low- and middle-income countries (see Pesquisa FAPESP issue nos. 302 and 303).
“Since the Newcastle virus originally infects chickens, it thrives in eggs,” said Krammer. This means it can be produced using the same technology that many countries, including Brazil, already use to manufacture influenza vaccines.
In the phase 1 human trial conducted in Thailand, used to assess the safety of the vaccine candidate, 210 volunteers were separated into six groups. Five were given two doses of varying volumes of the compound, either alone or combined with an adjuvant (a substance that enhances the immune response), with a four-week interval between doses. The sixth group was given two doses of an innocuous solution (placebo).
Two weeks after completing the immunization schedule, Krammer and his colleagues collected blood samples from the participants to compare the levels of antibodies generated by HXP-GPOVac against those produced by 20 people given the Pfizer/BioNTech vaccine and another 18 who had naturally recovered from infection by the novel coronavirus. The antibodies developed by the three groups were all able to neutralize the original strain of SARS-CoV-2 that appeared in Wuhan, China, in late 2019, and to a lesser extent, the Beta and Delta variants.
An initial evaluation presented in the journal eClinicalMedicine in March 2022 showed that HXP-GPOVac was safe and caused mild adverse events, such as pain at the application site in 63% of cases, fatigue in 35%, and headache or muscle pain in 32%. A slightly smaller proportion of these events, also mild, were observed among the 120 volunteers who participated in the phase 1 clinical trials of CoviVac in Vietnam. Pain at the injection site was experienced by 58% of participants, fatigue by 22%, headache by 21%, and muscle pain by 14%, according to preliminary data published in the journal Vaccine in June 2022.
In Brazil, ButanVac’s phase 1 trial, with 320 participants, has already been completed and the results analyzed by the Brazilian Health Regulatory Agency (ANVISA). Although no scientific article containing the trial results has been published, ANVISA has authorized the next stage to begin. “ButanVac proved to be highly immunogenic,” says Érique Peixoto de Miranda, clinical development medical manager at the Butantan Institute. “The binding and neutralizing antibody titers measured in the blood of recipients are similar to those of its two sister formulations being tested in Asia. This demonstrates a consistent effect.” Adverse events recorded in ButanVac’s phase 1 trial were also mild and similar to those observed in Thailand and Vietnam.
Despite using the same master viral strain and all being produced in eggs, the three formulations follow different procedures for production, quality control, and potency and stability testing. For this reason, ANVISA considers them different vaccine candidates and has not accepted data from the trials in Asia in place of ButanVac clinical data.
CARREÑO, J. M. et al. An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination. Science Translational Medicine. Feb. 15, 2023.
PITISUTTITHUM, P. et al. Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing Sars-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial. eClinicalMedicine. Mar. 2022.
DUC DANG, A. et al. Safety and immunogenicity of an egg-based inactivated Newcastle disease virus vaccine expressing Sars-CoV-2 spike: Interim results of a randomized, placebo-controlled, phase 1/2 trial in Vietnam. Vaccine. June 9, 2022.