Laboratorio Avi Mex SA de CV

Low- and middle-income countries face substantial challenges in immunizing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including high costs, limited access, and insufficient local manufacturing. To address these issues, we developed and locally manufactured the AVX/COVID-12 vaccine using a cost-effective Newcastle disease virus LaSota platform to express a stabilized SARS-CoV-2 spike protein (HexaPro-S). We evaluated the AVX/COVID-12 vaccine in a phase 2/3 parallel-group, double-blind, active-controlled, noninferiority trial with 4056 volunteers, demonstrating its safety, good tolerability, and ability to induce neutralizing antibodies against ancestral SARS-CoV-2 and the Omicron BA.2 and BA.5 variants. It also stimulated interferon-γ–producing CD8 + T cells and met the World Health Organization’s noninferiority criteria compared to AZ/ChAdOx-1-S. No vaccinated participants experienced severe disease, hospitalization, or death. These findings support the use of AVX/COVID-12 as a booster to help achieve and maintain population immunity while addressing global inequities in vaccine distribution, and it has been approved for adult booster use in Mexico.

The global inequity in the distribution of COVID-19 vaccines underscores the urgent need for innovative and cost-effective vaccine technologies to address access disparities and implement local manufacturing capabilities. This is essential for achieving and sustaining widespread immunity, and for ensuring timely protection of vulnerable populations during future booster campaigns in lower- middle income countries (LMICs).

To address this need, we conducted a phase II clinical trial to evaluate the safety and immunogenicity of the locally manufactured AVX/COVID-12 "Patria" (AVX) vaccine as a booster dose. The vaccine was administered either intramuscularly (IM) or intranasally (IN) to participants who had previously completed a vaccination regimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using adenoviral vector, inactivated virus, or mRNA-based vaccines. Participants with initial anti-spike IgG titers below 1,200 U/mL were included, allowing us to observe the booster effect induced by vaccination.

Both IM and IN immunization with AVX were found to be safe and well-tolerated. The vaccine induced a significant (>2.5-fold) increase in neutralizing antibodies against the ancestral Wuhan strain and variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was further supported by increased cellular production of interferon-gamma (IFN-γ), demonstrating a robust and multifaceted immune reaction.

The administration of AVX as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the ancestral Wuhan-1 strain but also against various VOCs. Its ability to enhance preexisting immune responses suggests a potential contribution to expanding and sustaining herd immunity within the population.

Growth conditions that bring about stress on Phaffia rhodozyma cells encourage the synthesis of astaxanthin, an antioxidant carotenoid, which protects cells against oxidative damage. Using P. rhodozyma cultures performed with and without copper limitation, we examined the kinetics of astaxanthin synthesis along with the expression of asy, the key astaxanthin synthesis gene, as well as aox, which encodes an alternative oxidase protein.

Copper deficiency had a detrimental effect on the rates of oxygen consumption and ethanol reassimilation at the diauxic shift. In contrast, copper deficiency prompted alcoholic fermentation under aerobic conditions and had a favorable effect on the astaxanthin content of cells, as well as on aox expression. Both cultures exhibited strong aox expression while consuming ethanol, but particularly when copper was absent.

We show that the induction of either astaxanthin production, aox expression, or aerobic fermentation exemplifies the crucial role that redox imbalance plays in triggering any of these phenomena. Based on our own results and data from others, we propose a mechanism that rationalizes the central role played by changes of respiratory activity, which lead to redox imbalances, in triggering both the short-term antioxidant response as well as fermentation in yeasts and other cell types.